尾村　誠一 （オムラ　セイイチ）

コミュニケーション情報 byコメンテータガイド

• コメント

  動物モデルを用いて多発性硬化症、ウイルス性心筋梗塞の発症、順序について、バイオインフォマティクスの手法により研究しています。

研究者情報

学位

• 博士（医学）（2010年03月 筑波大学）

ホームページURL

https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201601007400002221

科研費研究者番号

• 80462480

J-Global ID

• 201601007400002221

研究キーワード

• タイラーウイルス   実験的自己免疫性脳脊髄炎   バイオインフォマティクス   ウイルス性心筋炎   多発性硬化症   

現在の研究分野（キーワード）

動物モデルを用いて多発性硬化症、ウイルス性心筋梗塞の発症、順序について、バイオインフォマティクスの手法により研究しています。

研究分野

• ライフサイエンス / 分子生物学
• ライフサイエンス / 実験動物学
• ライフサイエンス / 細菌学
• ライフサイエンス / 免疫学
• ライフサイエンス / ウイルス学

経歴

• 2021年04月 - 現在  近畿大学医学部微生物学講座講師
• 2016年04月 - 2021年03月  近畿大学医学部微生物学講座助教
• 2010年04月 - 2016年03月  米国ルイジアナ州立大学医学部微生物学免疫学講座博士研究員
• 2008年07月 - 2010年03月  東京工業大学統合研究院ソリューション研究員
• 2004年08月 - 2008年06月  国立環境研究所環境健康研究領域研究員

学歴

• 2006年04月 - 2010年03月   筑波大学大学院   人間総合科学研究科   分子情報・生体統御医学専攻
• 2000年04月 - 2002年03月   広島大学大学院   先端物質科学研究科   分子生命機能科学専攻
• 1996年04月 - 2000年03月   広島大学   工学部   第三類（化学系）発酵工学課程

所属学協会

• 日本神経免疫学会   日本神経学会   American Society for Virology   

研究活動情報

論文

• Exploring the Role of Platelets in Virus-Induced Inflammatory Demyelinating Disease and Myocarditis

  Ijaz Ahmad; Seiichi Omura; Fumitaka Sato; Ah-Mee Park; Sundar Khadka; Felicity N. E. Gavins; Hiroki Tanaka; Motoko Y. Kimura; Ikuo Tsunoda

  International Journal of Molecular Sciences 25 6 3460 - 3460 2024年03月 [査読有り]
   

  Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a mouse model for two virus-induced organ-specific immune-mediated diseases. TMEV-induced demyelinating disease (TMEV-IDD) in the central nervous system (CNS) is a chronic inflammatory disease with viral persistence and an animal model of multiple sclerosis (MS) in humans. TMEV infection can also cause acute myocarditis with viral replication and immune cell infiltration in the heart, leading to cardiac fibrosis. Since platelets have been reported to modulate immune responses, we aimed to determine the role of platelets in TMEV infection. In transcriptome analyses of platelets, distinct sets of immune-related genes, including major histocompatibility complex (MHC) class I, were up- or downregulated in TMEV-infected mice at different time points. We depleted platelets from TMEV-infected mice by injecting them with platelet-specific antibodies. The platelet-depleted mice had significantly fewer viral antigen-positive cells in the CNS. Platelet depletion reduced the severities of TMEV-IDD and myocarditis, although the pathology scores did not reach statistical significance. Immunologically, the platelet-depleted mice had an increase in interferon (IFN)-γ production with a higher anti-TMEV IgG2a/IgG1 ratio. Thus, platelets may play roles in TMEV infection, such as gene expression, viral clearance, and anti-viral antibody isotype responses.
• Anti-Glycolipid Antibody Examination in Five EAE Models and Theiler’s Virus Model of Multiple Sclerosis: Detection of Anti-GM1, GM3, GM4, and Sulfatide Antibodies in Relapsing-Remitting EAE

  Kota Moriguchi; Yumina Nakamura; Ah-Mee Park; Fumitaka Sato; Motoi Kuwahara; Sundar Khadka; Seiichi Omura; Ijaz Ahmad; Susumu Kusunoki; Ikuo Tsunoda

  International Journal of Molecular Sciences 24 16 12937 - 12937 2023年08月 [査読有り][招待有り]
   

  Anti-glycolipid antibodies have been reported to play pathogenic roles in peripheral inflammatory neuropathies, such as Guillain–Barré syndrome. On the other hand, the role in multiple sclerosis (MS), inflammatory demyelinating disease in the central nervous system (CNS), is largely unknown, although the presence of anti-glycolipid antibodies was reported to differ among MS patients with relapsing-remitting (RR), primary progressive (PP), and secondary progressive (SP) disease courses. We investigated whether the induction of anti-glycolipid antibodies could differ among experimental MS models with distinct clinical courses, depending on induction methods. Using three mouse strains, SJL/J, C57BL/6, and A.SW mice, we induced five distinct experimental autoimmune encephalomyelitis (EAE) models with myelin oligodendrocyte glycoprotein (MOG)35–55, MOG92–106, or myelin proteolipid protein (PLP)139–151, with or without an additional adjuvant curdlan injection. We also induced a viral model of MS, using Theiler’s murine encephalomyelitis virus (TMEV). Each MS model had an RR, SP, PP, hyperacute, or chronic clinical course. Using the sera from the MS models, we quantified antibodies against 11 glycolipids: GM1, GM2, GM3, GM4, GD3, galactocerebroside, GD1a, GD1b, GT1b, GQ1b, and sulfatide. Among the MS models, we detected significant increases in four anti-glycolipid antibodies, GM1, GM3, GM4, and sulfatide, in PLP139–151-induced EAE with an RR disease course. We also tested cellular immune responses to the glycolipids and found CD1d-independent lymphoproliferative responses only to sulfatide with decreased interleukin (IL)-10 production. Although these results implied that anti-glycolipid antibodies might play a role in remissions or relapses in RR-EAE, their functional roles need to be determined by mechanistic experiments, such as injections of monoclonal anti-glycolipid antibodies.
• Adjuvant Injections Altered the Ileal and Fecal Microbiota Differently with Changes in Immunoglobulin Isotypes and Antimycobacterial Antibody Responses

  Sundar Khadka; Seiichi Omura; Fumitaka Sato; Ikuo Tsunoda

  International Journal of Molecular Sciences 24 3 2818 - 2818 2023年02月 [査読有り][招待有り]
   

  Alterations in the gut microbiota, “dysbiosis,” have been reported in autoimmune diseases, including multiple sclerosis (MS), and their animal models. Although the animal models were induced by injections of autoantigens with adjuvants, including complete Freund’s adjuvant (CFA) and pertussis toxin (PT), the effects of adjuvant injections on the microbiota are largely unknown. We aimed to clarify whether adjuvant injections could affect the microbiota in the ileum and feces. Using 16S rRNA sequencing, we found decreased alpha diversities of the gut microbiota in mice injected with CFA and PT, compared with naïve mice. Overall, microbial profiles visualized by principal component analysis demonstrated dysbiosis in feces, but not in the ileum, of adjuvant-injected mice, where the genera Lachnospiraceae NK4A136 group and Alistipes contributed to dysbiosis. When we compared the relative abundances of individual bacteria, we found changes in 16 bacterial genera in feces and seven genera in the ileum of adjuvant-injected mice, in which increased serum levels of antibody against mycobacteria (a component of CFA) and total IgG2c were correlated with the genus Facklamia. On the other hand, increased IgG1 and IgA concentrations were correlated with the genus Atopostipes. Therefore, adjuvant injections alone could alter the overall microbial profiles (i.e., microbiota) and individual bacterial abundances with altered antibody responses; dysbiosis in animal models could be partly due to adjuvant injections.
• Exploratory factor analysis determines latent factors in Guillain–Barré syndrome

  Seiichi Omura; Kazuaki Shimizu; Motoi Kuwahara; Miyuki Morikawa-Urase; Susumu Kusunoki; Ikuo Tsunoda

  Scientific Reports 12 1 21837  2022年12月 [査読有り]
   

  Abstract Exploratory factor analysis (EFA) has been developed as a powerful statistical procedure in psychological research. EFA’s purpose is to identify the nature and number of latent constructs (= factors) underlying a set of observed variables. Since the research goal of EFA is to determine what causes the observed responses, EFA is ideal for hypothesis-based studies, such as identifying the number and nature of latent factors (e.g., cause, risk factors, etc.). However, the application of EFA in the biomedical field has been limited. Guillain–Barré syndrome (GBS) is peripheral neuropathy, in which the presence of antibodies to glycolipids has been associated with clinical signs. Although the precise mechanism for the generation of anti-glycolipid antibodies is unclear, we hypothesized that latent factors, such as distinct autoantigens and microbes, could induce different sets of anti-glycolipid antibodies in subsets of GBS patients. Using 55 glycolipid antibody titers from 100 GBS and 30 control sera obtained by glycoarray, we conducted EFA and extracted four factors related to neuroantigens and one potentially suppressive factor, each of which was composed of the distinct set of anti-glycolipid antibodies. The four groups of anti-glycolipid antibodies categorized by unsupervised EFA were consistent with experimental and clinical findings reported previously. Therefore, we proved that unsupervised EFA could be applied to biomedical data to extract latent factors. Applying EFA for other biomedical big data may elucidate latent factors of other diseases with unknown causes or suppressing/exacerbating factors, including COVID-19.
• マウス胃のピロリ菌慢性感染は脳に神経炎症と遺伝子発現変化を誘導する

  朴 雅美; 尾村 誠一; 佐藤 文孝; 角田 郁生

  老年精神医学雑誌 33 増刊II 257 - 257 (株)ワールドプランニング 2022年11月
• MS3 異なる病型を示す多発性硬化症の動物モデルにおける抗糖脂質抗体の検討

  森口 幸太; 中村 優美和; 朴 雅美; 佐藤 文孝; 桑原 基; スンダル・カドカ; 尾村 誠一; イジャーズ・エフマド; 楠 進; 角田 郁生

  神経免疫学 27 1 164 - 164 (一社)日本神経免疫学会 2022年10月
• マウス胃のピロリ菌慢性感染は脳に神経炎症と遺伝子発現変化を誘導する

  朴 雅美; 尾村 誠一; 佐藤 文孝; 角田 郁生

  Dementia Japan 36 4 758 - 758 (一社)日本認知症学会 2022年10月
• 神経免疫疾患のバリア破綻の病態と治療 バリア(腸管バリア、BBB)破綻を伴うCNS免疫性疾患における脳内の「菌の定着colonization」の注意点

  角田 郁生; 朴 雅美; 尾村 誠一; 堀田 芙美香; 城 玲央奈; Sundar Khadka; Ijaz Ahmad; 森口 幸太; 佐藤 文孝

  神経免疫学 27 1 79 - 79 (一社)日本神経免疫学会 2022年10月
• Bacterial and fungal isolation from face masks under the COVID-19 pandemic.

  Ah-Mee Park; Sundar Khadka; Fumitaka Sato; Seiichi Omura; Mitsugu Fujita; Kazuki Hashiwaki; Ikuo Tsunoda

  Scientific reports 12 1 11361 - 11361 2022年07月 [査読有り]
   

  The COVID-19 pandemic has led people to wear face masks daily in public. Although the effectiveness of face masks against viral transmission has been extensively studied, there have been few reports on potential hygiene issues due to bacteria and fungi attached to the face masks. We aimed to (1) quantify and identify the bacteria and fungi attaching to the masks, and (2) investigate whether the mask-attached microbes could be associated with the types and usage of the masks and individual lifestyles. We surveyed 109 volunteers on their mask usage and lifestyles, and cultured bacteria and fungi from either the face-side or outer-side of their masks. The bacterial colony numbers were greater on the face-side than the outer-side; the fungal colony numbers were fewer on the face-side than the outer-side. A longer mask usage significantly increased the fungal colony numbers but not the bacterial colony numbers. Although most identified microbes were non-pathogenic in humans; Staphylococcus epidermidis, Staphylococcus aureus, and Cladosporium, we found several pathogenic microbes; Bacillus cereus, Staphylococcus saprophyticus, Aspergillus, and Microsporum. We also found no associations of mask-attached microbes with the transportation methods or gargling. We propose that immunocompromised people should avoid repeated use of masks to prevent microbial infection.
• Curdlan, a Microbial β-Glucan, Has Contrasting Effects on Autoimmune and Viral Models of Multiple Sclerosis

  Fumitaka Sato; Yumina Nakamura; Aoshi Katsuki; Sundar Khadka; Ijaz Ahmad; Seiichi Omura; Nicholas E. Martinez; Ikuo Tsunoda

  Frontiers in Cellular and Infection Microbiology 12 2022年02月 [査読有り]
   

  Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and axonal degeneration in the central nervous system (CNS). Bacterial and fungal infections have been associated with the development of MS; microbial components that are present in several microbes could contribute to MS pathogenesis. Among such components, curdlan is a microbial 1,3-β-glucan that can stimulate dendritic cells, and enhances T helper (Th) 17 responses. We determined whether curdlan administration could affect two animal models for MS: an autoimmune model, experimental autoimmune encephalomyelitis (EAE), and a viral model, Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD). We induced relapsing-remitting EAE by sensitizing SJL/J mice with the myelin proteolipid protein (PLP)_139-151 peptide and found that curdlan treatment prior to PLP sensitization converted the clinical course of EAE into hyperacute EAE, in which the mice developed a progressive motor paralysis and died within 2 weeks. Curdlan-treated EAE mice had massive infiltration of T cells and neutrophils in the CNS with higher levels of Th17 and Th1 responses, compared with the control EAE mice. On the other hand, in TMEV-IDD, we found that curdlan treatment reduced the clinical scores and axonal degeneration without changes in inflammation or viral persistence in the CNS. In summary, although curdlan administration exacerbated the autoimmune MS model by enhancing inflammatory demyelination, it suppressed the viral MS model with reduced axonal degeneration. Therefore, microbial infections may play contrasting roles in MS depending on its etiology: autoimmunity versus viral infection.
• Curcumin β-D-Glucuronide Modulates an Autoimmune Model of Multiple Sclerosis with Altered Gut Microbiota in the Ileum and Feces

  Sundar Khadka; Seiichi Omura; Fumitaka Sato; Kazuto Nishio; Hideaki Kakeya; Ikuo Tsunoda

  Frontiers in Cellular and Infection Microbiology 11 772962 - 772962 2021年12月 [査読有り][招待有り]
   

  We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose intravenous/intraperitoneal injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to alter the gut microbiota and immune responses, it is unclear whether the altered microbiota could be associated with inflammation in immune-mediated diseases, such as multiple sclerosis (MS). We aimed to determine whether CMG administration could affect the gut microbiota at three anatomical sites (feces, ileal contents, and the ileal mucosa), leading to suppression of inflammation in the central nervous system (CNS) in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE). We injected EAE mice with CMG, harvested the brains and spinal cords for histological analyses, and conducted microbiome analyses using 16S rRNA sequencing. CMG administration modulated EAE clinically and histologically, and altered overall microbiota compositions in feces and ileal contents, but not the ileal mucosa. Principal component analysis (PCA) of the microbiome showed that principal component (PC) 1 values in ileal contents, but not in feces, correlated with the clinical and histological EAE scores. On the other hand, when we analyzed the individual bacteria of the microbiota, the EAE scores correlated with significant increases in the relative abundance of two bacterial species at each anatomical site: Ruminococcus bromii and Blautia (Ruminococcus) gnavus in feces, Turicibacter sp. and Alistipes finegoldii in ileal contents, and Burkholderia spp. and Azoarcus spp. in the ileal mucosa. Therefore, CMG administration could alter the gut microbiota at the three different sites differentially in not only the overall gut microbiome compositions but also the abundance of individual bacteria, each of which was associated with modulation of neuroinflammation.
• プロドラッグ型クルクミンCMGによる腸内細菌叢変化と多発性硬化症自己免疫モデルの抑制(Curcumin monoglucuronide(CMG) affects the gut microbiota, suppressing an autoimmune model for multiple sclerosis)

  スンダル・カドカ; 尾村 誠一; 佐藤 文孝; 中村 優美和; 甲木 蒼紫; 崎山 奈美江; 朴 雅美; 西尾 和人; 掛谷 秀昭; 角田 郁生

  近畿大学医学雑誌 46 3-4 20A - 20A 2021年12月
• 多発性硬化症の成因最前線 ～多発性硬化症のタイラーウイルスモデルは神経炎症と心筋炎を誘導する～

  尾村誠一; 角田郁生

  Pharma Medica - The Review of Medicine and Pharmacology 39 8 67 - 71 2021年08月 [招待有り]
  
• 感染によって誘発される神経免疫病態 タイラーウイルスによる急性灰白脳脊髄炎・多発性硬化症動物モデル 分子相同性から腸内細菌叢まで

  角田 郁生; 尾村 誠一; 佐藤 文孝; 崎山 奈美江; Khadka Sundar; 中村 優美和; 朴 雅美; 藤田 貢

  神経免疫学 25 1 67 - 67 日本神経免疫学会 2020年10月
• プロドラッグ型クルクミンCMGによる実験的自己免疫性脳脊髄炎の抑制と小腸細菌叢変化

  佐藤 文孝; カドカ・スンダル; 尾村 誠一; 朴 雅美; 藤田 貢; 中村 優美和; 西尾 和人; 掛谷 秀昭; 角田 郁生

  神経免疫学 25 1 100 - 100 日本神経免疫学会 2020年10月
• Galectin-3 as a Therapeutic Target for NSAID-Induced Intestinal Ulcers

  Ah-Mee Park; Sundar Khadka; Fumitaka Sato; Seiichi Omura; Mitsugu Fujita; Daniel K. Hsu; Fu-Tong Liu; Ikuo Tsunoda

  Frontiers in Immunology 11 550366 - 550366 2020年09月 [査読有り]
   

  Non-steroidal anti-inflammatory drugs (NSAIDs) induce ulcers in the gastrointestinal tract, including the stomach and small intestine. NSAID-induced gastric ulcers can be prevented by taking acid-neutralizing/inhibitory drugs and cytoprotective agents. In contrast, there are no medicines to control NSAID-induced small intestinal ulcers, which are accompanied by a mucosal invasion of bacteria and subsequent activation of immune cells. Galectin-3 (Gal3), an endogenous lectin, has anti-microbial and pro-inflammatory functions. In the small intestine, since Gal3 is highly expressed in epithelial cells constitutively and macrophages inducibly, the Gal3 level can affect microbiota composition and macrophage activation. We hypothesized that the modulation of Gal3 expression could be beneficial in NSAID-induced intestinal ulcers. Using Gal3 knockout (Gal3KO) mice, we determined whether Gal3 could be a therapeutic target in NSAID-induced intestinal ulcers. Following the administration of indomethacin, an NSAID, we found that small intestinal ulcers were less severe in Gal3KO mice than in wild-type (WT) mice. We also found that the composition of intestinal microbiota was different between WT and Gal3KO mice and that bactericidal antibiotic polymyxin B treatment significantly suppressed NSAID-induced ulcers. Furthermore, clodronate, a macrophage modulator, attenuated NSAID-induced ulcers. Therefore, Gal3 could be an exacerbating factor in NSAID-induced intestinal ulcers by affecting the intestinal microbiota population and macrophage activity. Inhibition of Gal3 may be a therapeutic strategy in NSAID-induced intestinal ulcers. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03832946.
• Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation

  Seiichi Omura; Fumitaka Sato; Ah-Mee Park; Mitsugu Fujita; Sundar Khadka; Yumina Nakamura; Aoshi Katsuki; Kazuto Nishio; Felicity N. E. Gavins; Ikuo Tsunoda

  Frontiers in Immunology 11 1138  2020年07月 [査読有り]
  
• ガレクチン-3は腸内細菌叢に影響し、NSAIDsによる小腸潰瘍の増悪因子として働く

  朴 雅美; 尾村 誠一; 佐藤 文孝; 藤田 貢; 角田 郁生

  腸内細菌学雑誌 34 2 138 - 138 (公財)腸内細菌学会 2020年04月
• ネパールのHIV陽性患者における抗レトロウイルス薬療法の有効性(Efficacy of antiretroviral therapy in HIV positive patients in Nepal)

  Khadka Sundar; 尾村 誠一; 佐藤 文孝; 朴 雅美; 藤田 貢; 崎山 奈美江; 中村 優美和; 甲木 蒼紫; 角田 郁生

  近畿大学医学雑誌 44 3-4 17A - 17A 2019年12月
• ウイルス性脳脊髄炎モデルにおける中枢神経病態と腸内細菌叢との関連性

  尾村 誠一; 佐藤 文孝; 藤田 貢; 朴 雅美; カドカ・スンダル; 角田 郁生

  NEUROINFECTION 24 2 162 - 162 日本神経感染症学会 2019年09月
• MS/NMO1 多発性硬化症ウイルスモデルにおける腸内細菌叢の変化と中枢神経系炎症性脱髄病変との関連

  尾村 誠一; 佐藤 文孝; 藤田 貢; 朴 雅美; カドカ・スンダル; 角田 郁生

  神経免疫学 24 1 104 - 104 日本神経免疫学会 2019年09月
• 自己免疫性脳炎とてんかん ウイルス誘導性てんかん動物モデルと免疫系(Immune system and Theiler's virus-induced animal model for seizures/epilepsy)

  角田 郁生; 佐藤 文孝; 尾村 誠一; Khadka Sundar; 藤田 貢; 朴 雅美; 甲木 蒼紫; 中村 優美和; 崎山 奈美江; Lindeberg Felicia

  てんかん研究 37 2 391 - 391 2019年09月
• Neurolymphatic biomarkers of brain endothelial inflammatory activation: Implications for multiple sclerosis diagnosis

  Yun JW; Cvek U; Kilgore PCSR; Tsunoda I; Omura S; Sato F; Zivadinov R; Ramanathan M; Minagar A; Alexander JS

  Life Sciences 229 116 - 123 2019年07月 [査読有り]
  
• Basic Gene Expression Characteristics of Glioma Stem Cells and Human Glioblastoma.

  Daisuke Sakamoto; Toshinori Takagi; Mitsugu Fujita; Seiichi Omura; Yasunori Yoshida; Tomoko Iida; Shinichi Yoshimura

  Anticancer research 39 2 597 - 607 2019年02月 [査読有り]
   

  BACKGROUND: Glioma stem cells (GSCs) play important roles in the tumorigenesis of glioblastoma multiforme (GBM). Using a novel cellular bioinformatics pipeline, we aimed to characterize the differences in gene-expression profiles among GSCs, U251 (glioma cell line), and a human GBM tissue sample. MATERIALS AND METHODS: Total RNA was extracted from GSCs, U251 and GBM and microarray analysis was performed; the data were then applied to the bioinformatics pipeline consisting of a principal component analysis (PCA) with factor loadings, an intracellular pathway analysis, and an immunopathway analysis. RESULTS: The PCA clearly distinguished the three groups. The factor loadings of the PCA suggested that v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), dipeptidyl-peptidase 4 (DPP4), and macrophage migration-inhibitory factor (MIF) contribute to the stemness of GSCs. The intracellular pathway and immunopathway analyses provided relevant information about the functions of representative genes in GSCs. CONCLUSION: The newly-developed cellular bioinformatics pipeline was a useful method to clarify the similarities and differences among samples.
• Bioinformatics Analyses Determined the Distinct CNS and Peripheral Surrogate Biomarker Candidates Between Two Mouse Models for Progressive Multiple Sclerosis.

  Seiichi Omura; Fumitaka Sato; Nicholas E Martinez; Ah-Mee Park; Mitsugu Fujita; Nikki J Kennett; Urška Cvek; Alireza Minagar; J Steven Alexander; Ikuo Tsunoda

  Frontiers in immunology 10 516 - 516 2019年 [査読有り]
   

  Previously, we have established two distinct progressive multiple sclerosis (MS) models by induction of experimental autoimmune encephalomyelitis (EAE) with myelin oligodendrocyte glycoprotein (MOG) in two mouse strains. A.SW mice develop ataxia with antibody deposition, but no T cell infiltration, in the central nervous system (CNS), while SJL/J mice develop paralysis with CNS T cell infiltration. In this study, we determined biomarkers contributing to the homogeneity and heterogeneity of two models. Using the CNS and spleen microarray transcriptome and cytokine data, we conducted computational analyses. We identified up-regulation of immune-related genes, including immunoglobulins, in the CNS of both models. Pro-inflammatory cytokines, interferon (IFN)-γ and interleukin (IL)-17, were associated with the disease progression in SJL/J mice, while the expression of both cytokines was detected only at the EAE onset in A.SW mice. Principal component analysis (PCA) of CNS transcriptome data demonstrated that down-regulation of prolactin may reflect disease progression. Pattern matching analysis of spleen transcriptome with CNS PCA identified 333 splenic surrogate markers, including Stfa2l1, which reflected the changes in the CNS. Among them, we found that two genes (PER1/MIR6883 and FKBP5) and one gene (SLC16A1/MCT1) were also significantly up-regulated and down-regulated, respectively, in human MS peripheral blood, using data mining.
• Theiler’s virus-mediated immunopathology in the CNS and heart: Roles of organ-specific cytokine and lymphatic responses

  Omura S; Kawai E; Sato F; Martinez NE; Minagar A; Al-Kafahi M; Yun JW; Cvek U; Trutschl M; Alexander JS; Tsunoda I

  Frontiers in Immunology 9 2018年12月 [査読有り][招待有り]
  
• IL-1β reduces cardiac lymphatic muscle contraction via COX-2 and PGE2 induction: Potential role in myocarditis

  Mahmoud Al-Kofahi; Seiichi Omura; Ikuo Tsunoda; Fumitaka Sato; Felix Becker; Felicity N.E. Gavins; Matthew D. Woolard; Christopher Pattillo; David Zawieja; Mariappan Muthuchamy; Anatoliy Gashev; Israa Shihab; Mohamed Ghoweba; Pierre-Yves Von der Weid; Yuping Wang; J. Steven Alexander

  Biomedicine & Pharmacotherapy 107 1591 - 1600 2018年11月 [査読有り]
   

  The role of lymphatic vessels in myocarditis is largely unknown, while it has been shown to play a key role in other inflammatory diseases. We aimed to investigate the role of lymphatic vessels in myocarditis using in vivo model induced with Theiler's murine encephalomyelitis virus (TMEV) and in vitro model with rat cardiac lymphatic muscle cells (RCLMC). In the TMEV model, we found that upregulation of a set of inflammatory mediator genes, including interleukin (IL)-1β, tumor necrosis factor (TNF)-αand COX-2 were associated with disease activity. Thus, using in vitro collagen gel contraction assays, we decided to clarify the role(s) of these mediators by testing contractility of RCLMC in response to IL-1β and TNF-α individually and in combination, in the presence or absence of: IL-1 receptor antagonist (Anakinra); cyclooxygenase (COX) inhibitors inhibitors (TFAP, diclofenac and DuP-697). IL-1β impaired RCLMC contractility dose-dependently, while co-incubation with both IL-1β and TNF-α exhibited synergistic effects in decreasing RCLMC contractility with increased COX-2 expression. Anakinra maintained RCLMC contractility; Anakinra blocked the mobilization of COX-2 induced by IL-1β with or without TNF-α. COX-2 inhibition blocked the IL-1β-mediated decrease in RCLMC contractility. Mechanistically, we found that IL-1β increased prostaglandin (PG) E2 release dose-dependently, while Anakinra blocked IL-1β mediated PGE2 release. Using prostaglandin E receptor 4 (EP4) receptor antagonist, we demonstrated that EP4 receptor blockade maintained RCLMC contractility following IL-1β exposure. Our results indicate that IL-1β reduces RCLMC contractility via COX-2/PGE2 signaling with synergistic cooperation by TNF-α. These pathways may help provoke inflammatory mediator accumulation within the heart, driving progression from acute myocarditis into dilated cardiomyopathy.
• Metallothionein I as a direct link between therapeutic hematopoietic stem/progenitor cells and cerebral protection in stroke

  Helen K. Smith; Seiichi Omura; Shantel A. Vital; Felix Becker; Elena Y. Senchenkova; Gaganpreet Kaur; Ikuo Tsunoda; Shayn M. Peirce; Felicity N. E. Gavins

  FASEB Journal 32 5 2381 - 2394 2018年05月 [査読有り]
   

  Stroke continues to be a leading cause of death and disability worldwide, yet effective treatments are lacking. Previous studies have indicated that stem-cell transplantation could be an effective treatment. However, little is known about the direct impact of transplanted cells on injured brain tissue. We wanted to help fill this knowledge gap and investigated effects of hematopoietic stem/progenitor cells (HSPCs) on the cerebral microcir-culation after ischemia-reperfusion injury (I/RI). Treatment of HSPCs in I/RI for upto 2 wk after cerebral I/RI led to decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation, and reduced cerebral leukocyte adhesion. Confocal microscopy and fluorescence-activated cell sorting analyses showed transplanted HSPCs emigrate preferentially into ischemic cortex brain parenchyma. We isolated migrated HSPCs from the brain using RNA sequencing to investigate the transcriptome, we found metallothionein (MT, particularly MT-I) transcripts were dramatically up-regulated. Finally, to confirm the significance of MT, we ex-ogenously administered MT-I after cerebral I/RI and found that it produced neuroprotection in a manner similar to HSPC treatment. These findings provide novel evidence that the mechanism through which HSPCs promote repair after stroke maybe via direct action of HSPC-derived MT-I and could therefore be exploited as a useful therapeutic strategy for stroke.
• Immunoregulation of Theiler’s virus-induced demyelinating disease by glatiramer acetate without suppression of antiviral immune responses

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Tierra Range; Lesya Ekshyyan; Alireza Minagar; J. Steven Alexander; Ikuo Tsunoda

  Archives of Virology 163 5 1279 - 1284 2018年05月 [査読有り]
   

  While most disease-modifying drugs (DMDs) regulate multiple sclerosis (MS) by suppressing inflammation, they can potentially suppress antiviral immunity, causing progressive multifocal leukoencephalopathy (PML). The DMD glatiramer acetate (GA) has been used for MS patients who are at high risk of PML. We investigated whether GA is safe for use in viral infections by using a model of MS induced by infection with Theiler’s murine encephalomyelitis virus (TMEV). Treatment of TMEV-infected mice with GA neither enhanced viral loads nor suppressed antiviral immune responses, while it resulted in an increase in the Foxp3/Il17a ratio and IL-4/IL-10 production. This is the first study to suggest that GA could be safe for MS patients with a proven viral infection.
• 次世代シークエンシングを用いた多発性硬化症ウイルスモデルの解析；リンパ管分子発現低下が病気の進行に関連する

  尾村誠一; 佐藤文孝; 藤田貢; 朴雅美; J. Steven Alexander; Phillip; C.S.R. Kilgore; rska Cvek; 角田郁生

  Neuroinfection 23 1 114 - 120 日本神経感染症学会 2018年04月 [査読有り][招待有り]
   

  多発性硬化症(MS)の発症要因はいまだ確定していないが、ウイルス感染がその一つと考えられている。MSの病理学的特徴は中枢神経系(CNS)への免疫細胞浸潤であり、接着分子の発現増加と血液脳関門の破綻が寄与している。一方、侵入した免疫細胞のCNSからの退出機序は不明であったが、近年CNS内リンパ管の存在が報告され、その役割が注目されている。本稿ではMSのウイルス感染モデルであるタイラーウイルス誘導性脱髄疾患マウスを用い、その脊髄トランスクリプトームデータのバイオインフォマティクス解析により、CNS内リンパ管の病態への寄与を検討した。タイラーウイルス感染群と対照群の接着分子、血液脳関門関連分子、リンパ管分子発現データを用いた主成分分析により、リンパ管分子の発現低下がリンパ球のCNSからの退出遅延に寄与することが示唆された。(著者抄録)
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• ギラン・バレー症候群における抗糖脂質抗体産生に関連する潜在因子の探索型因子分析による同定

  尾村誠一; 清水和秋; 桑原基; 森川みゆき; 藤田貢; 朴雅美; 佐藤文孝; PEDIO Erika; 楠進; 角田郁生

  Neuroimmunology 23 1 103 - 103 日本神経免疫学会 2018年
• T-bet, but not Gata3, overexpression is detrimental in a neurotropic viral infection

  Fumitaka Sato; Eiichiro Kawai; Nicholas E. Martinez; Seiichi Omura; Ah-Mee Park; Satoru Takahashi; Keigyou Yoh; Ikuo Tsunoda

  SCIENTIFIC REPORTS 7 2017年09月 [査読有り]
   

  Intracerebral Theiler's murine encephalomyelitis virus (TMEV) infection in mice induces inflammatory demyelination in the central nervous system. Although C57BL/6 mice normally resistant to TMEV infection with viral clearance, we have previously demonstrated that ROR gamma t-transgenic (tg) C57BL/6 mice, which have Th17-biased responses due to ROR gamma t overexpression in T cells, became susceptible to TMEV infection with viral persistence. Here, using T-bet-tg C57BL/6 mice and Gata3-tg C57BL/6 mice, we demonstrated that overexpression of T-bet, but not Gata3, in T cells was detrimental in TMEV infection. Unexpectedly, T-bet-tg mice died 2 to 3 weeks after infection due to failure of viral clearance. Here, TMEV infection induced splenic T cell depletion, which was associated with lower anti-viral antibody and T cell responses. In contrast, Gata3-tg mice remained resistant, while Gata3-tg mice had lower IFN-gamma and higher IL-4 production with increased anti-viral IgG1 responses. Thus, our data identify how overexpression of T-bet and Gata3 in T cells alters anti-viral immunity and confers susceptibility to TMEV infection.
• Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer’s disease: 10 pitfalls of microbiome studies

  Ah-Mee Park; Seiichi Omura; Mitsugu Fujita; Fumitaka Sato; Ikuo Tsunoda

  Clinical and Experimental Neuroimmunology 8 3 215 - 232 2017年08月 [査読有り]
   

  Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD). Following H. pylori infection, pro-inflammatory T helper (Th)1 and Th17 immune response are initially induced to eradicate bacteria. However, H. pylori evades the host immune response by inducing Th2 cells and regulatory T cells (Tregs) that produce anti-inflammatory interleukin (IL)-10. Suppression of anti-bacterial Th1/Th17 cells by Tregs may enhance gastric H. pylori propagation, followed by a cascade reaction involving vitamin B12 and folic acid malabsorption, plasma homocysteine elevation, and reactive oxygen species induction. This can damage the blood-brain barrier (BBB), leading to accumulation of amyloid-β in the brain, a hallmark of AD. On the other hand, this suppression of pro-inflammatory Th1/Th17 responses to H. pylori has protective effects on the hosts, since it prevents uncontrolled gastritis as well as suppresses the induction of encephalitogenic Th1/Th17 cells, which can mediate neuroinflammation in MS. The above scenario may explain why chronic H. pylori infection is positively associated with AD, while it is negatively associated with MS. Lastly, we list "10 pitfalls of microbiota studies", which will be useful for evaluating and designing clinical and experimental microbiota studies.
• Computational analysis determined the homogeneities and heterogeneities between two distinct EAE models for progressive multiple sclerosis

  Sendai Conference 2017 2017年07月 [査読有り]
  
• ウイルス感染によって誘導される“軸索型”多発性硬化症動物モデル:インサイド‐アウト・モデル

  角田郁生; 尾村誠一; 佐藤文孝; 崎山奈美江; PARK Ah‐Mee; 藤田貢

  Neuroinfection 22 1 28‐35 - 35 日本神経感染症学会 2017年04月 

  多発性硬化症(multiple sclerosis、MS)は中枢神経系の炎症性脱髄と軸索障害を主体とする神経変性疾患であり、全世界では200万人以上、日本では約1万人のMS患者が存在する。MS発症の原因としてはウイルス感染説と自己免疫説が提唱されている。その動物実験モデルとして、前者に対してはタイラーウイルス誘導性脱髄疾患[Theiler's murine encephalomyelitis virus(TMEV)-induced demyelinating disease、TMEV-IDD]が、後者に対しては実験的自己免疫性脳脊髄炎(experimental autoimmune encephalomyelitis、EAE)が、それぞれ頻用されている。両者ともT細胞が病変形成に関与するが、MS様病変である脱髄と軸索変性の進展様式は両者間で異なる。TMEV-IDDでは、病変は神経線維の内側(インサイド)の軸索障害に始まり、外側(アウトサイド)の髄鞘障害(=脱髄)へと進展する(インサイド-アウト・モデル)。一方、EAEでは外側の髄鞘障害が先行し、続いて内側の軸索障害が誘導される(アウトサイド-イン・モデル)。ヒトMSの病理像では、インサイド-アウト・モデルとアウトサイド-イン・モデルそれぞれに合致する病理像が報告されており、前者は"軸索型"MSといえるものであり、後者の古典的"脱髄型"MSとは異なる。また両者の病理像が同一個体でみられるMS症例も存在する。すなわち"インサイド-アウト"と"アウトサイド-イン"の進展様式は相反するものではなく、むしろ共存して悪循環を形成し病態進行に寄与しうると推測される。この悪循環を断つ方法としては、1)炎症抑制、2)軸索保護、3)軸索変性の抑制(ウイルス感染の場合は、ウイルス増殖抑制による)の三つが考えられる。理論的には、この悪循環のいずれかのステップに介入する治療法がMSの進行抑制を可能にする。実際、MS治療に作用点の異なる複数の薬剤が有効であるという臨床データが、MS症例の多くで前述二つの進展様式が共存しうることを示唆する。(著者抄録)
• Viral infection activates myelin-specific T cells, triggering MS-like CNS inflammatory demyelination

  Sato F; Omura S; Park A. M; Fujita M; Stokes K; Tsunoda I

  Journal of the Neurological Sciences 381 1057 - 1058 2017年 [査読有り]
  
• Bioinformatics analyses determined the CNS and peripheral lymphoid surrogate biomarker candidates between two distinct EAE models for progressive multiple sclerosis

  Omura S; Sato F; Martinez N. E; Park A. M; Cvek U; Alexander J. S; Tsunoda I

  Journal of the Neurological Sciences 381 794 - 795 2017年 [査読有り]
  
• Influx and efflux of immune cells in the central nervous system

  Mitsugu Fujita; Seiichi Omura; Fumitaka Sato; Ah-Mee Park; Ikuo Tsunoda

  Anatomy & Physiology: Current Research 7 274  2017年 [査読有り]
  
• Three immune-mediated disease models induced by Theiler’s virus: multiple sclerosis, seizures, and myocarditis

  Ikuo Tsunoda; Fumitaka Sato; Seiichi Omura; Mitsugu Fujita; Namie Sakiyama; Ah-Mee Park

  Clinical and Experimental Neuroimmunology 7 4 330 - 345 2016年11月 [査読有り]
   

  Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis. Interestingly, acquired immunity plays an effector role in the MS model, whereas innate immunity appears to contribute to the development of seizures. Recently, we have established the third TMEV-induced disease model, a mouse model for viral myocarditis, using C3H mice. TMEV-induced myocarditis is a triphasic disease, which mimics human myocarditis; phase I, mediated by viral replication in the heart and innate immunity; phase II, mediated by acquired immunity; and phase III, resulted from cardiac fibrosis. The genetic susceptibility to the aforementioned three models (MS, seizures and myocarditis) differs among mouse strains. We have compared and contrasted the three models induced by one single pathogen, TMEV, particularly in regard to the roles of T helper cells and natural killer T cells, which will give an insight into how interactions between the immune system and the host's genetic background determine the tissue tropism of virus and the development of virus-induced organ-specific immunopathology.
• Upregulation of lymphatic markers and vascular adhesion molecules in CNS RNAseq transcriptome of a viral model for multiple sclerosis

  The 6th Annual International Society for Neurovascular Disease (ISNVD) Scientific Meeting 2016年04月 [査読有り]
  
• Exposure assessment and heart rate variability monitoring in workers handling titanium dioxide particles: a pilot study

  Sahoko Ichihara; Weihua Li; Seiichi Omura; Yuji Fujitani; Ying Liu; Qiangyi Wang; Yusuke Hiraku; Naomi Hisanaga; Kenji Wakai; Xuncheng Ding; Takahiro Kobayashi; Gaku Ichihara

  Journal of Nanoparticle Research 18 3 1 - 14 2016年03月 [査読有り]
   

  © 2016, Springer Science+Business Media Dordrecht. Titanium dioxide (TiO2) particles are used for surface coating and in a variety of products such as inks, fibers, food, and cosmetics. The present study investigated possible respiratory and cardiovascular effects of TiO2 particles in workers exposed to this particle at high concentration in a factory in China. The diameter of particles collected on filters was measured by scanning electron microscopy. Real-time size-dependent particle number concentration was monitored in the nostrils of four workers using condensation particle counter and optical particle counter. Electrocardiogram was recorded using Holter monitors for the same four workers to record heart rate variability. Sixteen workers underwent assessment of the respiratory and cardiovascular systems. Mass-based individual exposure levels were also measured with personal cascade impactors. The primary particle diameter ranged from 46 to 562 nm. Analysis of covariance of the pooled data of the four workers showed that number of particles with a diameter <300 nm was associated positively with total number of N–N and negatively with total number of increase or decrease in successive RR intervals greater than 50 ms (RR50+/−) or percentage of RR 50+/− that were parameters of parasympathetic function. The total mass concentration was 9.58–30.8 mg/m3 during work, but significantly less before work (0.36 mg/m3). The clear abnormality in respiratory function was not observed in sixteen workers who had worked for 10 months to 13 years in the factory. The study showed that exposure to particles with a diameter <300 nm might affect HRV in workers handling TiO2 particles. The results highlight the need to investigate the possible impact of exposure to nano-scaled particles on the autonomic nervous system.
• Neuropathogenesis of Zika Virus Infection : Potential Roles of Antibody-Mediated Pathology.

  Ikuo Tsunoda; Seiichi Omura; Fumitaka Sato; Susumu Kusunoki; Mitsugu Fujita; Ah-Mee Park; Faris Hasanovic; Richard Yanagihara; Satoshi Nagata

  Acta medica Kinki University 41 2 37 - 52 2016年 [査読有り]
   

  Zika virus (ZIKV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Flavivirus, family Flaviviridae, which includes many human and animal pathogens, such as dengue virus (DENV), West Nile virus, and Japanese encephalitis virus. In the original as well as subsequent experimental and clinical reports, ZIKV seems to have moderate neurotropism (in animal models) and neurovirulence (in human fetuses), but no neuroinvasiveness (in human adults). Intrauterine ZIKV infection (viral pathology) has been linked to an increased incidence of microcephaly, while increased Guillain-Barré syndrome (GBS) following ZIKV infection is likely immune-mediated (immunopathology). Clinically, in ZIKV infection, antibodies against other flaviviruses, such as DENV, have been detected; these antibodies can cross-react with ZIKV without ZIKV neutralization. In theory, such non-neutralizing antibodies are generated at the expense of decreased production of neutralizing antibodies ("antigenic sin"), leading to poor viral clearance, while the non-neutralizing antibodies can also enhance viral replication in Fc receptor (FcR)-bearing cells via antibody-dependent enhancement (ADE). Here, we propose three potential roles of the antibody-mediated pathogenesis of ZIKV infection: 1) cross-reactive antibodies that recognize ZIKV and neural antigens cause GBS; 2) ZIKV-antibody complex is transported transplacentally via neonatal FcR (FcRn), resulting in fetal infection; and 3) ZIKV-antibody complex is taken up at peripheral nerve endings and transported to neurons in the central nervous system (CNS), by which the virus can enter the CNS without crossing the blood-brain barrier.
• "Microglial nodules" and "newly forming lesions" may be a Janus face of early MS lesions; implications from virus-induced demyelination, the Inside-Out model

  Fumitaka Sato; Nicholas E. Martinez; Elaine Cliburn Stewart; Seiichi Omura; J. Steven Alexander; Ikuo Tsunoda

  BMC NEUROLOGY 15 1 2015年10月 [査読有り]
   

  Background: Although the precise mechanism of initial lesion development in multiple sclerosis ( MS) remains unclear, two different neuropathological findings have been reported as a potential early pathology of MS: "microglial nodules" and "newly forming lesions", both of which contain neither T cell infiltration nor demyelination. In microglial nodules, damaged axons were associated with a small number of aggregated macrophages/microglia, while oligodendrocyte apoptosis was a characteristic in newly forming lesions. However, is the presence of" microglial nodules" and "oligodendrogliopathy" mutually exclusive? Might these two different observations be the same neuropathology (as proposed by the concept, "preactive lesions"), but interpreted differently based on the different theories of early MS lesion development, using different staining methods? Discussion: Since two studies are looking at two distinct aspects of early MS pathogenesis (one focused on axons and the other on oligodendrocytes), in a sense, one can say that these two studies are complementary. On the other hand, experimentally, Wallerian degeneration (WD) has been demonstrated to induce both microglial nodules and oligodendrocyte apoptosis in the central nervous system (CNS). Here, when encephalitogenic T cells are present in the periphery in both autoimmune and viral models of MS, induction of WD in the CNS has been shown to result in the recruitment of T cells along the degenerated tract, leading to demyelination (Inside-Out model). These experimental findings are consistent with early MS pathology described by both "microglial nodules" and "newly forming lesions". Conclusions: The differences between the two neuropathological findings may be based on the preference of staining methods, where one group observed axonal and microglial pathology and the other observed oligodendrocyte apoptosis; a Janus face that is looked at from the two different sides.
• Blood circulating microparticle species in relapsing-remitting and secondary progressive multiple sclerosis. A case-control, cross sectional study with conventional MRI and advanced iron content imaging outcomes

  J. S. Alexander; R. Chervenak; B. Weinstock-Guainan; I. Tsunoda; M. Ramanathan; N. Martinez; S. Omura; F. Sato; G. V. Chaitanya; A. Minagar; J. McGee; M. H. Jennings; C. Monceaux; F. Becker; U. Cvek; M. Trutschl; R. Zivadinov

  JOURNAL OF THE NEUROLOGICAL SCIENCES 355 1-2 84 - 89 2015年08月 [査読有り]
   

  Background: Although multiple sclerosis (MS) is thought to represent an excessive and inappropriate immune response to several central nervous system (CNS) autoantigens, increasing evidence also suggests that MS may also be a neurovascular inflammatory disease, characterized by endothelial activation and shedding of cell membrane microdomains known as 'microparticles' into the circulation. Objective: To investigate the relationships between these endothelial biomarkers and MS. Methods: We examined the relative abundance of CD31(+)/PECAM-1, CD51(+)CD61(+) (alpha V-3) and CD54(+) (ICAM-1) bearing microparticles in sera of healthy individuals, patients with relapsing remitting MS, and secondary-progressive MS. We also investigated the correlation among circulating levels of different micropartide species in MS with conventional MRI (12- and T1-lesion volumes and brain atrophy), as well as novel MR modalities [assessment of iron content on susceptibility-weighted imaging (SWI)-filtered phase]. Results: Differences in circulating micropartide levels were found among MS groups, and several microparticle species (CD31(+)/CD51(+)/CD61(+)/CD54(+)) were found to correlate with conventional MRI and SWI features of MS. Conclusion: These results indicate that circulating microparticles' profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses. (C) 2015 Elsevier B.V. All rights reserved.
• Organ-specific protective role of NKT cells in virus-induced inflammatory demyelination and myocarditis depends on mouse strain

  Eiichiro Kawai; Fumitaka Sato; Seiichi Omura; Nicholas E. Martinez; Pratap C. Reddy; Masaru Taniguchi; Ikuo Tsunoda

  JOURNAL OF NEUROIMMUNOLOGY 278 174 - 184 2015年01月 [査読有り]
   

  Theiler's murine encephalomyelitis virus (TMEV) can induce demyelination or myocarditis insusceptible mouse strains. A deficiency of NKT cells exacerbated TMEV-induced demyelinating disease (TMEV-IDD) in SJL/J and BALB/c mice. In C579L/6 background, however, NKT-cell-deficient J alpha 18 KO mice remained as resistant to TMEV-IDD as wild-type mice. Echocardiography and histology showed that J alpha 18 KO mice developed more severe myocarditis (greater T cell infiltration and fibrosis) than wild-type mice, suggesting a protective role of NKT cells in myocarditis in C57BL/6 mice. J alpha 18 KO mice had higher cardiac viral RNA and anti-viral antibody titers, but had lower lymphoproliferation and IL-4 and IL-10 production. (C) 2014 Elsevier B.V. All rights reserved.
• Th17-biased RORγt transgenic mice become susceptible to a viral model for multiple sclerosis

  Nicholas E Martinez; Fumitaka Sato; Eiichiro Kawai; Seiichi Omura; Satoru Takahashi; Keigyou Yoh; Ikuo Tsunoda

  Brain, Behavior and Immunity 43 86 - 97 2015年01月 [査読有り]
   

  In a viral model for multiple sclerosis (MS), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), both immune-mediated tissue damage (immunopathology) and virus persistence have been shown to cause pathology. T helper (Th) 17 cells are a Th cell subset, whose differentiation requires the transcription factor retinoic acid-related orphan receptor (ROR) gamma t, secrete pro-inflammatory cytokines, including IL-17, and can antagonize Th1 cells. Although Th17 cells have been shown to play a pathogenic role in immune-mediated diseases or a protective role in bacterial and fungal infections, their role in viral infections is unclear. Using newly established Th17-biased ROR gamma t Tg mice, we tested whether Th17 cells could play a pathogenic or protective role in TMEV-IDD by contributing to immunopathology and/or by modulating anti-viral Th1 immune responses. While TMEV-infected wild-type littermate C57BL/6 mice are resistant to TMEV-IDD, ROR gamma t Tg mice developed inflammatory demyelinating lesions with virus persistence in the spinal cord. TMEV-infected ROR gamma t Tg mice had higher levels of IL-17, lower levels of interferon-gamma, and fewer CD8(+) T cells, without alteration in overall levels of anti-viral lymphoproliferative and antibody responses, compared with TMEV-infected wild-type mice. This suggests that a Th17-biased "gain-of-function" mutation could increase susceptibility to virus-mediated demyelinating diseases. (C) 2014 Elsevier Inc. All rights reserved.
• Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler's virus infection

  Fumitaka Sato; Seiichi Omura; Eiichiro Kawai; Nicholas E. Martinez; Madan M. Acharya; Pratap C. Reddy; Ganta V. Chaitanya; J. Steven Alexander; Ikuo Tsunoda

  CELLULAR IMMUNOLOGY 292 1-2 85 - 93 2014年11月 [査読有り]
   

  We established a novel model of myocarditis induced with Theiler's murine encephalomyelitis virus (TMEV), which has been used as a viral model for multiple sclerosis and seizure/epilepsy. Following TMEV infection, C3H mice developed severe myocarditis with T cell infiltration, while C57BL/6 mice had mild lesions and SJL/J mice had no inflammation in the heart. In C3H mice, myocarditis was divided into three phases: acute viral, subacute immune, and chronic fibrotic phases. Using toll-like receptor (TLR) 4-deficient C3H mice, we found that interleukin (IL)-6, IL-17, TLR4, and anti-viral immune responses were associated with myocarditis susceptibility. (C) 2014 Elsevier Inc. All rights reserved.
• ROR gamma t, but not T-bet, overexpression exacerbates an autoimmune model for multiple sclerosis

  Nicholas E. Martinez; Fumitaka Sato; Seiichi Omura; Eiichiro Kawai; Satoru Takahashi; Keigyou Yoh; Ikuo Tsunoda

  JOURNAL OF NEUROIMMUNOLOGY 276 1-2 142 - 149 2014年11月 [査読有り]
   

  Th17 cells play an important role in multiple sclerosis (MS) and its autoimmune model, experimental autoimmune encephalomyelitis (EAE). However, studies have not addressed how enhanced Th17 immune responses can affect demyelinating diseases. We induced EAE with MOG in ROR gamma t transgenic C57BL/6 mice that overexpress a Th17 inducing transcription factor. ROR gamma t transgenic mice developed more severe EAE than wild-type mice with more robust anti-MOG Th17 immune responses. In contrast, mice overexpressing T-bet, a Th1-inducing transcription factor, were resistant to EAE. Therefore, a genetic bias toward Th17 immune responses could contribute to CNS immunopathology. (C) 2014 Elsevier B.V. All rights reserved.
• Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler's virus infection

  Fumitaka Sato; Seiichi Omura; Eiichiro Kawai; Nicholas E. Martinez; Madan M. Acharya; Pratap C. Reddy; Ganta V. Chaitanya; J. Steven Alexander; Ikuo Tsunoda

  CELLULAR IMMUNOLOGY 292 1-2 85 - 93 2014年11月 [査読有り]
   

  We established a novel model of myocarditis induced with Theiler's murine encephalomyelitis virus (TMEV), which has been used as a viral model for multiple sclerosis and seizure/epilepsy. Following TMEV infection, C3H mice developed severe myocarditis with T cell infiltration, while C57BL/6 mice had mild lesions and SJL/J mice had no inflammation in the heart. In C3H mice, myocarditis was divided into three phases: acute viral, subacute immune, and chronic fibrotic phases. Using toll-like receptor (TLR) 4-deficient C3H mice, we found that interleukin (IL)-6, IL-17, TLR4, and anti-viral immune responses were associated with myocarditis susceptibility. (C) 2014 Elsevier Inc. All rights reserved.
• RORγt, but not T-bet, overexpression exacerbates an autoimmune model for multiple sclerosis

  Nicholas E. Martinez; Fumitaka Sato; Seiichi Omura; Eiichiro Kawai; Satoru Takahashi; Keigyou Yoh; Ikuo Tsunoda

  Journal of Neuroimmunology 276 1-2 142 - 149 2014年11月 [査読有り]
   

  Th17 cells play an important role in multiple sclerosis (MS) and its autoimmune model, experimental autoimmune encephalomyelitis (EAE). However, studies have not addressed how enhanced Th17 immune responses can affect demyelinating diseases. We induced EAE with MOG in ROR gamma t transgenic C57BL/6 mice that overexpress a Th17 inducing transcription factor. ROR gamma t transgenic mice developed more severe EAE than wild-type mice with more robust anti-MOG Th17 immune responses. In contrast, mice overexpressing T-bet, a Th1-inducing transcription factor, were resistant to EAE. Therefore, a genetic bias toward Th17 immune responses could contribute to CNS immunopathology. (C) 2014 Elsevier B.V. All rights reserved.
• Protective and Detrimental Roles for Regulatory T Cells in a Viral Model for Multiple Sclerosis

  Nicholas E. Martinez; Fridrik Karlsson; Fumitaka Sato; Eiichiro Kawai; Seiichi Omura; Alireza Minagar; Matthew B. Grisham; Ikuo Tsunoda

  BRAIN PATHOLOGY 24 5 436 - 451 2014年09月 [査読有り]
   

  Multiple sclerosis (MS) has been proposed to be an immune-mediated disease in the central nervous system (CNS) that can be triggered by virus infections. In Theiler's murine encephalomyelitis virus (TMEV) infection, during the first week (acute stage), mice develop polioencephalomyelitis. After 3 weeks (chronic stage), mice develop immune-mediated demyelination with virus persistence, which has been used as a viral model for MS. Regulatory T cells (Tregs) can suppress inflammation, and have been suggested to be protective in immune-mediated diseases, including MS. However, in virus-induced inflammatory demyelination, although Tregs can suppress inflammation, preventing immune-mediated pathology, Tregs may also suppress antiviral immune responses, leading to more active viral replication and/or persistence. To determine the role and potential translational usage of Tregs in MS, we treated TMEV-infected mice with ex vivo generated induced Tregs (iTregs) on day 0 (early) or during the chronic stage (therapeutic). Early treatment worsened clinical signs during acute disease. The exacerbation of acute disease was associated with increased virus titers and decreased immune cell recruitment in the CNS. Therapeutic iTreg treatment reduced inflammatory demyelination during chronic disease. Immunologically, iTreg treatment increased interleukin-10 production from B cells, CD4(+) T cells and dendritic cells, which may contribute to the decreased CNS inflammation.
• Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

  Seiichi Omura; Eiichiro Kawai; Fumitaka Sato; Nicholas E. Martinez; Ganta V. Chaitanya; Phoebe A. Rollyson; Urska Cvek; Marjan Trutschl; J. Steven Alexander; Ikuo Tsunoda

  CIRCULATION-CARDIOVASCULAR GENETICS 7 4 444 - 454 2014年08月 [査読有り]
   

  Background-Myocarditis is an inflammatory disease of the cardiac muscle and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into 3 phases: the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the 3 phases. Theiler's murine encephalomyelitis virus belongs to the genus Cardiovirus and can cause myocarditis in susceptible mouse strains. Methods and Results-Using this novel model for viral myocarditis induced with Theiler's murine encephalomyelitis virus, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray to identify the biomarker candidates that can discriminate the 3 phases. Using C3H mice infected with Theiler's murine encephalomyelitis virus on 4, 7, and 60 days post infection, we conducted bioinformatics analyses, including principal component analysis and k-means clustering of microarray data, because our traditional cardiac and serum assays, including 2-way comparison of microarray data, did not lead to the identification of a single biomarker. Principal component analysis separated heart samples clearly between the groups of 4, 7, and 60 days post infection. Representative genes contributing to the separation were as follows: 4 and 7 days post infection, innate immunity-related genes, such as Irf7 and Cxcl9; 7 and 60 days post infection, acquired immunity-related genes, such as Cd3g and H2-Aa; and cardiac remodeling-related genes, such as Mmp12 and Gpnmb. Conclusions-Sets of molecules, not single molecules, identified by unsupervised principal component analysis, were found to be useful as phase-specific biomarkers.
• Phase-specific cardiac biomarkers and blood surrogate markers for a mouse model of myocarditis induced by cardiovirus

  The 33rd Annual Meeting of the American Society for Virology (ASV) 2014年06月 [査読有り]
  
• COMPUTATIONAL MULTIVARIATE ANALYSES FOR PHASE-SPECIFIC BIOMARKER IDENTIFICATION IN NOVEL IN VIVO AND IN VITRO VIRAL MYOCARDITIS MODELS INDUCED BY CARDIOVIRUS

  Fereidoon Shafiei; Seiichi Omura; Eiichiro Kawai; Fumitaka Sato; Nicholas E. Martinez; Viromi Fernando; Liam Morris; J. Steven Lexander; Urska Cvek; Marjan Trutschl; Ikuo Tsunoda

  JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 63 12 A971 - A971 2014年04月 [査読有り]
  
• Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

  Viromi Fernando; Seiichi Omura; Fumitaka Sato; Eiichiro Kawai; Nicholas E. Martinez; Sadie Faith Elliott; Keigyou Yoh; Satoru Takahashi; Ikuo Tsunoda

  INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 15 2 1700 - 1718 2014年02月 [査読有り]
   

  T helper (Th)2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS). This is mainly based on loss-of-function studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE), using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (gain-of-function approach) could alter EAE, the approach of novel GATA binding protein 3 (GATA3)-transgenic (tg) mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL)-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon- and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.
• Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature

  Ganta Vijay Chaitanya; Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Alireza Minagar; Murali Ramanathan; Bianca Weinstock Guttman; Robert Zivadinov; Ikuo Tsunoda; Jonathan S. Alexander

  JOURNAL OF NEUROINFLAMMATION 10 2013年10月 [査読有り]
   

  Background: Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin(+) (lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the inflamed neurovasculature. Methods: We assessed the protein levels of lymphatic vessel endothelial hyaluronan receptor and podoplanin, which are specific to the lymphatic system and prospero-homeobox protein-1, angiopoietin-2, vascular endothelial growth factor-D, vascular endothelial growth factor receptor-3, which are expressed by both lymphatic endothelium and neurons. Levels of these proteins were measured in postmortem brains and sera from MS patients, in the myelin proteolipid protein (PLP)-induced EAE and Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating disease (TMEV-IDD) mouse models and in cell culture models of inflamed neurovasculature. Results and conclusions: Intense staining for LYVE-1 was found in neurons of a subset of MS patients using immunohistochemical approaches. The lymphatic protein, podoplanin, was highly expressed in perivascular inflammatory lesions indicating signaling cross-talks between inflamed brain vasculature and lymphatic proteins in MS. The profiles of these proteins in MS patient sera discriminated between relapsing remitting MS from secondary progressive MS and normal patients. The in vivo findings were confirmed in the in vitro cell culture models of neuroinflammation.
• Natural Killer T Cells Play Protective Roles in Cardiovirus-Induced Myocarditis by Inducing Anti-Viral and Regulatory Cytokines

  Fumitaka Sato; Seiichi Omura; Nicholas E. Martinez; Eiichiro Kawai; Sadie F. Pearson; Viromi Fernando; Madan M. Acharya; Ganta V. Chaitanya; J. Steven Alexander; Maureen N. Ajuebor; Masaru Taniguchi; Ikuo Tsunoda

  CIRCULATION RESEARCH 113 4 2013年08月 [査読有り]
  
• Computational analysis of microarray gene expression patterns discriminates the acute viral versus subacute immune phases of myocarditis induced by cardiovirus

  The 32nd Annual Meeting of the American Society for Virology (ASV) 2013年07月 [査読有り]
  
• Immunopathological patterns from EAE and Theiler's virus infection: Is multiple sclerosis a homogenous 1-stage or heterogenous 2-stage disease?

  Martinez NE; Sato F; Omura S; Minagar A; Alexander JS; Tsunoda I

  Pathophysiology : the official journal of the International Society for Pathophysiology 20 1 71 - 84 2013年02月 [査読有り]
   

  Multiple sclerosis (MS) is a disease which can presents in different clinical courses. The most common form of MS is the relapsing-remitting (RR) course, which in many cases evolves into secondary progressive (SP) disease. Autoimmune models such as experimental autoimmune encephalomyelitis (EAE) have been developed to represent the various clinical forms of MS. These models along with clinico-pathological evidence obtained from MS patients have allowed us to propose '1-stage' and '2-stage' disease theories to explain the transition in the clinical course of MS from RR to SP. Relapses in MS are associated with pro-inflammatory T helper (Th) 1/Th17 immune responses, while remissions are associated with anti-inflammatory Th2/regulatory T (Treg) immune responses. Based on the '1-stage disease' theory, the transition from RR to SP disease occurs when the inflammatory immune response overwhelms the anti-inflammatory immune response. The '2-stage disease' theory proposes that the transition from RR to SP-MS occurs when the Th2 response or some other responses overwhelm the inflammatory response resulting in the sustained production of anti-myelin antibodies, which cause continuing demyelination, neurodegeneration, and axonal loss. The Theiler's virus model is also a 2-stage disease, where axonal degeneration precedes demyelination during the first stage, followed by inflammatory demyelination during the second stage.
• Determination of Phase-specific Biomarkers of Viral Myocarditis Induced by Theiler's virus Using Multivariate Analyses of Viral Genome, Troponin, Transcriptome and Echocardiography Data

  Kawai Eiichiro; Omura Seiichi; Sato Fumitaka; Martinez Nicholas E; Fernando Viromi; Rollyson Phoebe; Cvek Urska; Trutschl Marjan; Tsunoda Ikuo

  Circulation Research 113 4 2013年 [査読有り]
  
• Th17 bias renders mice susceptible to a viral model for multiple sclerosis

  Nicholas E. Martinez; Fumitaka Sato; Seiichi Omura; Eiichiro Kawai; Satoru Takahashi; Keigyou Yoh; Ikuo Tsunoda

  JOURNAL OF NEUROIMMUNOLOGY 253 1-2 105 - 106 2012年12月 [査読有り]
  
• Detrimental Role of Toll-Like Receptor 4 in Cardiovirus-Induced Myocarditis

  Fumitaka Sato; Seiichi Omura; Nicholas E. Martinez; Eiichiro Kawai; Ganta V. Chaitanya; Jonathan S. Alexander; Ikuo Tsunoda

  CIRCULATION RESEARCH 111 4 2012年08月 [査読有り]
  
• Chemokine and Autophagy-Related Genes in Novel In Vivo and In Vitro Models for Viral Myocarditis

  Eiichiro Kawai; Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Ganta V. Chaitanya; William C. Claycomb; J. S. Alexander; Ikuo Tsunoda

  CIRCULATION RESEARCH 111 4 2012年08月 [査読有り]
  
• Upregulation of chemokines and interferon-associated genes in a novel model for myocarditis induced by cardiovirus infection

  31st The American Society for Virology (ASV) Annual Meeting 2012年07月 [査読有り]
  
• Regulatory T cells and Th17 cells in viral infections: implications for multiple sclerosis and myocarditis

  Nicholas E. Martinez; Fumitaka Sato; Eiichiro Kawai; Seiichi Omura; Robert P. Chervenak; Ikuo Tsunoda

  FUTURE VIROLOGY 7 6 593 - 608 2012年06月 [査読有り]
   

  In immune-mediated diseases, Treg and proinflammatory Th17 cells have been suggested to play either suppressor (beneficial) or effector (detrimental) roles, respectively. Tissue damage in viral infections can be caused by direct viral replication or immunopathology. Viral replication can be enhanced by anti-inflammatory responses and suppressed by proinflammatory responses. However, Tregs could suppress proinflammatory responses, reducing immunopathology, while Th17 cell-induced inflammation may enhance immunopathology. Here, the roles of Treg and Th17 cells depend on whether tissue damage is caused by direct virus replication or immunopathology, which differ depending on the virus, disease stage and host immune background. Although the precise mechanisms of tissue damage in multiple sclerosis and myocarditis are unclear, both viral replication and immune effector cells have been proposed to cause pathogenesis. Personalized medicine that alters the balance between Treg and Th17 cells may ameliorate viral pathology during infections.
• Curdlan, a Th17 Cell Inducer, Plays Contrasting Roles in a Viral Model for Multiple Sclerosis

  Fumitaka Sato; Nicholas Martinez; Seiichi Omura; Steve Alexander; Alireza Minagar; Ikuo Tsunoda

  NEUROLOGY 78 2012年04月 [査読有り]
  
• Regulatory T Cells Play Contrasting Roles in a Viral Model for Multiple Sclerosis

  Nicholas E. Martinez; Fridrik Karlsson; Fumitaka Sato; Seiichi Omura; Alireza Minagar; Mathew B. Grisham; Ikuo Tsunoda

  ANNALS OF NEUROLOGY 70 S90 - S91 2011年10月 [査読有り]
  
• Roles of Th1 and Th17 cells in autoimmune and viral models for relapsing-remitting versus progressive multiple sclerosis

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Nikki J. Kennett; Ikuo Tsunoda

  63rd Annual Meeting of the American Academy of Neurology 76 9 A460 - A460 2011年03月 [査読有り]
  
• Heterogeneity versus homogeneity of multiple sclerosis

  Fumitaka Sato; Nicholas E. Martinez; Seiichi Omura; Ikuo Tsunoda

  EXPERT REVIEW OF CLINICAL IMMUNOLOGY 7 2 165 - 167 2011年03月 [査読有り]
   

  The 10th International Congress of Neuroimmunology, including the 10th European School of Neuroimmunology Course, was held by the International Society of Neuroimmunology in Sitges (Barcelona, Spain) on 26-30 October 2010. The conference covered a wide spectrum of issues and challenges in both basic science and clinical aspects of neuroimmunology. Data and ideas were shared through a variety of programs, including review talks and poster sessions. One of the topics of the congress was whether multiple sclerosis is a homogenous or heterogenous disease, clinically and pathologically, throughout its course.
• Microarray analysis of gene expression in rat alveolar epithelial cells exposed to fractionated organic extracts of diesel exhaust particles

  Seiichi Omura; Eiko Koike; Takahiro Kobayashi

  TOXICOLOGY 262 1 65 - 72 2009年07月 [査読有り]
   

  Diesel exhaust particles (DEP) affect health adversely. Our previous studies revealed that DEP extracts up-regulated expression of genes related to drug metabolism, antioxidant enzymes, cell cycle/apoptosis and coagulation, and in addition, n-hexane soluble fraction (n-HSF) of DEP extracts contains aliphatic and polycyclic aromatic hydrocarbons, and n-hexane insoluble fraction (n-HISF) contains oxygenated compounds and has strong oxidative property. However, the relationship between the properties of chemicals in DEP extracts and the gene expression has not been fully elucidated. Here, we used a microarray analysis to identify and characterize genes whose expression is regulated by exposure to fractions of DEP extracts. A dichloromethane-soluble fraction (DMSF) of DEP was further fractionated into n-HSF and n-HISF. We exposed rat alveolar epithelial (SV40T2) cells to these fractions (30 mu g/ml) for 6 h and identified regulated genes. DMSF predominantly up-regulated genes associated with drug metabolism (Cyp1a1, Gsta3), oxidative stress response (HO-1, Srxn1) and cell cycle/apoptosis (Okl38). Genes up-regulated by n-HSF were mainly associated with drug metabolism (Cyplal, Gsta3). The genes up-regulated by n-HISF included antioxidant enzymes (HO-1, Srxnl); genes response to cell damage, such as those functioning in cell cycle regulation or apoptosis (Okl38); and genes in coagulation pathways. Our present results suggested that n-HSF and n-HISF regulated characteristic genes which respond to chemical properties of each fraction. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
• Arsenite-induced thymus atrophy is mediated by cell cycle arrest: A characteristic downregulation of E2F-Related genes revealed by a microarray approach

  Keiko Nohara; Kana Ao; Yoshimi Miyamoto; Takehiro Suzuki; Satoru Imaizumi; Yukiyo Tateishi; Seiichi Omura; Chiharu Tohyama; Takahiro Kobayashi

  TOXICOLOGICAL SCIENCES 101 2 226 - 238 2008年02月 [査読有り]
   

  Thymus atrophy is induced by a variety of chemicals, including environmental contaminants and is used as a sensitive index to detect their adverse effects on lymphocytes. In the present study we adopted a toxicogenomics approach to identify the pathways that mediate the atrophy induced by arsenite. We also analyzed gene expression changes observed in the course of thymus atrophy by 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), dexamethasone (DEX), and estradiol (E2), to determine whether arsenite induces atrophy by activating an arsenite-specific pathway or the same pathways as other chemicals. These compounds were intraperitoneally administered to C57BL/6 mice at doses that reduce thymus weight by approximately 30% within 3 days, and gene expression changes in the thymus 24 h after the administration were analyzed by using microarrays and real-time PCR. The microarray analysis showed that arsenite specifically downregulates a variety of E2F target genes that are involved in cell cycle progression. The same genes were also downregulated when mouse B-cell lymphoma A20 cells were exposed to arsenite. Arsenite exposure of the A20 cells was confirmed to induce cell cycle arrest, mainly in the G(1) phase, and reduce cell number. Cell cycle arrest in the G(1) phase was also confirmed to occur in the thymocytes of the arsenite-exposed mice. These results indicate that arsenite induces thymus atrophy through E2F-dependent cell cycle arrest. The results of this study also show that analysis of gene expression in thymuses is a useful method of obtaining clues to the pathways that mediate the effects of atrophy-inducing chemicals.
• No effects of estrogen receptor overexpression on gonadal sex differentiation and reversal in medaka fish

  T Kawamura; S Omura; S Sakai; Yamashita, I

  ZOOLOGICAL SCIENCE 20 1 43 - 47 2003年01月 [査読有り]
   

  In order to elucidate a possible role of estrogen receptor in the gonadal sex differentiation and the sex reversal with sex steroids, we examined for the formation of testis or ovary in transgenic medaka fish overexpressing the medaka estrogen receptor under the constitutive medaka beta-actin promoter. The transgenic fish underwent the genetically determined gonadal differentiation and showed the same sex-reversal rates as those of wild-type non-transgenic fish after treatments with estrogen and androgen. These results present invaluable data to reconsider the role of estrogen receptor in the gonadal sex determination.
• Estrogen inhibits development of yolk veins and causes blood clotting in transgenic medaka fish overexpressing estrogen receptor

  T Kawamura; S Sakai; S Omura; R Hori-e; T Kawahara; M Kinoshita; Yamashita, I

  ZOOLOGICAL SCIENCE 19 12 1355 - 1361 2002年12月 [査読有り]
   

  We established three transgenic medaka fish lines overexpressing the medaka estrogen receptor under the constitutive medaka beta-actin promoter. The transgenic embryos became hypersensitive to estrogens (17beta-estradiol and 17alpha-ethinylestradiol), and failed to develop yolk veins while blood clots formed in the blood island within 3 days after exposure to the estrogens. The embryos developed normally if exposed to estrogen after an early neurula stage, suggesting that the sensitive stage is before neurulation. The developmental defects were recovered by incubation with an anti-estrogen, tamoxifen. These results indicate that activation of estrogen receptor caused the estrogen-induced, developmental defects. Our results show that the transgenic embryos can be used to assay the blood clotting activity of estrogenic compounds in vivo.

書籍

• Animal models for multiple sclerosis. In: Neuroinflammation (2nd edition)

  Sato F; Omura S; Martinez NE; Tsunoda I (担当:分担執筆範囲:pp. 37-72)Elsevier 2018年
• Role of CD4+ T lymphocytes in pathophysiology of multiple sclerosis. In: Multiple Sclerosis: A Mechanistic View

  Sato F; Omura S; Jaffe SL; Tsunoda I (担当:分担執筆範囲:pp. 41-69)Elsevier 2015年11月
• Animal models for multiple sclerosis. In: Neuroinflammation (Elsevier Insights)

  Sato F; Omura S; Martinez NE; Tsunoda I (担当:分担執筆範囲:pp. 55-79)Elsevier 2010年12月 ISBN: 0123849136 540

講演・口頭発表等

• Complete Freund’s adjuvant treatment changed the ileal and fecal microbiota differently with altered immunoglobulin isotype and anti-tuberculosis antibody responses  [通常講演]

  スンダル・カドカ; 尾村誠一; 佐藤文孝; イジャーズ・エフマド; 角田郁生

  第51回日本免疫学会学術集会 2022年12月 ポスター発表
• Roles of anti-glycolipid antibodies in different animal models of multiple sclerosis with distinct clinical courses  [通常講演]

  Sato F; Nakamura Y; Moriguchi K; Park A-M; Kuwahara M; Omura S; Khadka S; Ahmad I; Kusunoki S; Tsunoda I

  第51回日本免疫学会学術集会 2022年12月 口頭発表（一般）
• Platelets play a detrimental role in an animal model of viral myocarditis  [通常講演]

  Ahmad I; Sato F; Omura S; Khadka S; Park A-M; Gavins FNE; Tsunoda I

  第69回日本ウイルス学会学術集会 口頭発表（一般）
• Curcumin monoglucuronide (CMG) treatment alters the gut microbiota, regulating an autoimmune model for multiple sclerosis  [通常講演]

  Omura S; Khadka S; Sato F; Nakamura Y; Nishio K; Kakeya H; Tsunoda I

  2021 International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2021) 2021年12月 口頭発表（招待・特別）
• Curcumin monoglucuronide (CMG) suppresses autoimmune model of multiple sclerosis via altered gut microbiota  [通常講演]

  Khadka S; Omura S; Sato F; Nishio K; Kakeya H; Tsunoda I

  第50回日本免疫学会学術集会 口頭発表（一般）
• Potential roles of IgA in the central nervous system in a viral model of multiple sclerosis  [通常講演]

  Sato F; Omura S; Park A-M; Khadka S; Nakamura Y; Katsuki A; Nishio K; Gavins FNE; Tsunoda I

  第50回日本免疫学会学術集会 口頭発表（一般）
• タイラーウイルスによる急性灰白脳脊髄炎・多発性硬化症動物モデル：分子相同性から腸内細菌叢まで  [通常講演]

  角田郁生; 尾村誠一; 佐藤文孝; 崎山奈美江; Sundar Khadka; 中村優美和; 朴雅美; 藤田貢

  第32回日本神経免疫学会学術集会 口頭発表（一般）
• ガレクチン-3は腸内細菌叢に影響し，NSAIDsによる小腸潰瘍の増悪因子として働く  [通常講演]

  朴雅美; 尾村誠一; 佐藤文孝; 藤田貢; 角田郁生

  第24回腸内細菌学会学術集会 口頭発表（一般）
• ウイルス性脳脊髄炎モデルにおける中枢神経病態と腸内細菌叢との関連性  [通常講演]

  尾村誠一; 佐藤文孝; 藤田貢; 朴雅美; スンダル・カドカ; 角田郁生

  第24回日本神経感染症学会総会学術大会 2019年10月 口頭発表（一般）
• 多発性硬化症ウイルスモデルにおける腸内細菌叢の変化と中枢神経系炎症性脱髄病変との関連  [通常講演]

  尾村誠一; 佐藤文孝; 藤田貢; 朴雅美; スンダル・カドカ; 角田郁生

  第31回日本神経免疫学会学術集会 2019年09月 口頭発表（一般）
• 多発性硬化症ウイルスモデルにおける中枢神経系炎症性病態と腸内細菌叢変化との関連性の検討  [通常講演]

  尾村誠一; 佐藤文孝; 朴雅美; 藤田貢; 角田郁生

  第23回腸内細菌学会 2019年06月 口頭発表（一般） 東京 公益財団法人 腸内細菌学会
  
• Communication between CNS and gut microbiota in a viral model for multiple sclerosis  [通常講演]

  Seiichi Omura; Kazuto Nishio; Ikuo Tsunoda

  The 1st International Symposium on Chemical Communication (ISCC2019) 2019年01月 ポスター発表
• Bioinformatics analyses identified phase-specific heart biomarkers and blood surrogate markers for a mouse model of viral myocarditis  [通常講演]

  Seiichi Omura; Fumitaka Sato; Ah-Mee Park; Mitsugu Fujita; J. Steven Alexander; Phillip CSR Kilgore; Urska Cvek; Ikuo Tsunoda

  Research and Industry Day (RAID) 2018 Conference 2018年10月 ポスター発表
• ギラン・バレー症候群における抗糖脂質抗体産生に関連する潜在因子の探索型因子分析による同定  [通常講演]

  尾村誠一; 清水和秋; 桑原基; 森川みゆき; 藤田貢; 朴雅美; 佐藤文孝; Erika Pedio; 楠進; 角田郁生

  第30回日本神経免疫学会学術集会 2018年09月 口頭発表（一般）
• Distinct sets of anti-glycolipid antibodies are associated with latent factors in Guillain-Barré syndrome by exploratory factor analysis  [通常講演]

  尾村誠一; 清水和秋; 桑原基; 森川みゆき; 藤田貢; 朴雅美; 佐藤文孝; 楠進; 角田郁生

  第14回国際神経免疫学会年会 2018年08月 口頭発表（一般）
• Bioinformatics analyses identified phase-specific heart biomarkers and blood surrogate markers for a mouse model of viral myocarditis  [通常講演]

  Seiichi Omura; Fumitaka Sato; Ah-Mee Park; Mitsugu Fujita; J. Steven Alexander; Phillip CSR Kilgore; Urska Cvek; Ikuo Tsunoda

  Louisiana Biomedical Research Network (LBRN) 16th Annual Meeting 2018年01月 ポスター発表
• 次世代シークエンシングを用いたウイルス性脳脊髄炎モデルの解析； リンパ管分子発現低下が免疫細胞の中枢神経内停滞に関連する  [通常講演]

  尾村誠一; 佐藤文孝; 藤田貢; 朴雅美; J. Steven Alexander、Phillip; C.S.R. Kilgore; rška Cvek; 角田郁生

  第22回日本神経感染症学会総会・学術大会 2017年10月 口頭発表（一般）
• Computational analysis determined the homogeneities and heterogeneieties between two distinct EAE models for progressive multiple sclerosis  [招待講演]

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Ah-Mee Park; Mitsugu Fujita; Phillip; C.S.R. Kilgore; Urska Cvek; Marjan Trutschl; Alireza Minagar; J. Steven Alexander; Ikuo Tsunoda

  7th Sendai Conference 2017年07月 口頭発表（一般）
• Upregulation of lymphatic markers and vascular adhesion molecules in CNS RNAseq transcriptome of a viral model for multiple sclerosis  [通常講演]

  Seiichi Omura; Fumitaka Sato; J. Steven Alexander, Phillip; C.S.R. Kilgore; Urska Cvek; Marjan Trutschl; Ikuo Tsunoda

  The 6th Annual International Society for Neurovascular Disease (ISNVD) Scientific Meeting 2016年04月 口頭発表（一般）
• Phase-specific cardiac biomarkers and blood surrogate markers for a mouse model of myocarditis induced by cardiovirus  [通常講演]

  Seiichi Omura; Fumitaka Sato; Eiichiro Kawai; Nicholas E. Martinez; Urska Cvek; Marjan Trutschl; J. Steven Alexander; Ikuo Tsunoda

  The 33rd Annual Meeting of the American Society for Virology (ASV) 2014年06月 口頭発表（一般）
• Brain biomarkers and spleen surrogate markers for primary progressive MS models  [通常講演]

  Seiichi Omura; Urska Cvek; Marjan Trutschl; Fumitaka Sato; Nicholas E. Martinez; Eiichiro Kawai; Viromi Fernando; Liam A. Morris; Madan M. Acharya; Fereidoon Shafiei; J. Steven Alexander; Ikuo Tsunoda

  International Workshop and Oral Presentation: MS Model 1, the 55th Annual Meeting of the Japanese Society of Neurology 2014年05月 口頭発表（一般）
• Computational analysis of microarray gene expression patterns discriminates the acute viral versus subacute immune phases of myocarditis induced by cardiovirus  [通常講演]

  Seiichi Omura; Fumitaka Sato; Eiichiro Kawai; Nicholas E. Martinez; Sadie F. Pearson; Phoebe Rollyson; Urska Cvek; Marjan Trutschl; Ikuo Tsunoda

  The 32nd Annual Meeting of the American Society for Virology (ASV) 2013年07月 口頭発表（一般）
• 工業ナノマテリアルの職業暴露評価における課題  [通常講演]

  市原 学; 小林 隆弘; 藤谷 雄二; 尾村 誠一; 市原 佐保子

  日本毒性学会学術年会 2013年 

  ナノテクノロジーは，並行して発展してきた分子生物学との融合を通じ新しい学術分野と革新的な技術を生み出すことが期待されている。ナノテクノロジー全体の中で，工業ナノマテリアルはその第一段階を形成するものである。一方，工業ナノマテリアルの健康，環境への影響，安全性についての研究は十分とは言えない。なかでもヒト健康へのリスク評価は優先順位の高い課題である。暴露評価はハザード評価と統合され，リスクを評価するために用いられる。工業ナノマテリアルに暴露された労働者を対象とした疫学コホート研究を立ち上げる構想が国際的にも議論されているが，その基盤としても暴露評価は重要な課題となっている。暴露評価におけるナノマテリアルに特異的な問題の一つは用量計測基準として何を選ぶかということである。この問題に関して国際的なコンセンサスはまだ得られていない。ナノマテリアルの個数，表面積が生体分子との反応性に貢献していると考えられていることから，従来の重量濃度に基づく計測基準が，ナノマテリアルの暴露を定義する上で十分かどうか疑問がある。走査式モビリティーパーティクルサイザー（SMPS）によりナノ領域を含む粒子を分級し連続的にモニターすることが可能であるが，高価で可動性に問題があり，労働現場でより簡易にナノ粒子を測定する機器の開発の必要性が唱えられてきた。米国国立労働安全衛生研究所は凝集粒子カウンター（CPC）と光散乱粒子計測装置（OPC）の併用を提案している。また，比較的安価で小型化されたSMPS，あるいは新しい小型計測機器も開発されている。長期の累積的な暴露の評価には多くの困難が伴う場合があることも指摘しなければならない。生体試料を用いた内部暴露評価のためにバイオロジカルモニタリング法の開発も求められ，そのためには様々な分野の研究者の共同が必要である。
• Upregulation of chemokines and interferon-associated genes in a novel model for myocarditis induced by cardiovirus infection  [通常講演]

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Ganta V. Chaitanya; William C. Claycomb; J. Steven Alexander; Ikuo Tsunoda

  The 31st Annual Meeting of the American Society for Virology (ASV) 2012年07月 口頭発表（一般）
• System biology analysis of microarray data from animal models for relapsing-remitting versus primary progressive multiple sclerosis  [通常講演]

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Nikki J. Kennett; J. Steven Alexander; Ikuo Tsunoda

  The 23rd Annual Meeting of the Japanese Society for Neuroimmunology 2011年09月 口頭発表（一般）
• Roles of Th1 and Th17 cells in autoimmune and viral models for relapsing-remitting versus progressive multiple sclerosis  [通常講演]

  Seiichi Omura; Fumitaka Sato; Nicholas E. Martinez; Nikki J. Kennett; Ikuo Tsunoda

  The 63rd Annual Meeting of the American Academy of Neurology 2011年04月 口頭発表（一般）
• Analysis of gene expression in the heart of rat following short-term exposure to diesel exhaust emitted during high-idling condition  [通常講演]

  Seiichi Omura; Yuji Fujitani; Takahiro Kobayashi

  The 50th Annual Meeting of the Japanese Society for Atmospheric Environment 2009年09月 口頭発表（一般）
• Gene expression profiling of rat lung following inhalation exposure of nanoparticle-rich diesel exhaust  [通常講演]

  Seiichi Omura; Yuji Fujitani; Hirotoshi Shima; Takahiro Kobayashi

  The 129th Annual Meeting of the Pharmaceutical Society of Japan 2009年03月 口頭発表（一般）
• Microarray analysis of gene expression profiling in rat alveolar epithelial cells exposed to diesel exhaust nanoparticles  [通常講演]

  Seiichi Omura; Eiko Koike; Yuji Fujitani; Takahiro Kobayashi

  The 47th Annual Meeting of the Japanese Society for Atmospheric environment 2006年09月 口頭発表（一般）
• Microarray analysis of gene expression profiling in heart and lung of rat exposed to diesel exhaust particles emitted during high-idling condition  [通常講演]

  Seiichi Omura; Hirotoshi Shima; Yuji Fujitani; Hajime Aoyagi; Takahiro Kobayashi

  The 47th Annual Meeting of the Japanese Society for Atmospheric environment 2006年09月 口頭発表（一般）
• Microarray analysis of gene expression profiling in rat alveolar epithelial cells exposed to fractionated organic extract of diesel exhaust particles  [通常講演]

  Seiichi Omura; Eiko Koike; Takahiro Kobayashi

  The 46th Annual Meeting of the Japanese Society for Atmospheric environment 2005年09月 口頭発表（一般）

MISC

• IgA抗体欠損は実験的自己免疫性脳脊髄炎を軽減させる

  佐藤文孝; 城玲央奈; 森口幸太; グエン コン・タン; エフマド イジャーズ; 尾村誠一; 朴雅美; 安達貴弘; 角田郁生 Neuroimmunology 28 (1) 2023年
• 多発性硬化症ウイルスモデルにおける中枢神経系炎症性病態と腸内細菌叢変化との関連性の検討

  尾村誠一; 佐藤文孝; 朴雅美; 藤田貢; 角田郁生 腸内細菌学雑誌 33 (2) 113 -113 2019年04月
• ピコルナウイルス誘導性急性脊髄炎モデルにおける腸内細菌叢と中枢神経遺伝子発現の変化

  佐藤文孝; 尾村誠一; 朴雅美; 藤田貢; SUNDAR Khadka; 西尾和人; 角田郁生 日本ウイルス学会学術集会プログラム・予稿集(Web) 67th 2019年
• 多発性硬化症における中枢神経系と腸内細菌叢のコミュニケーション

  角田郁生; 尾村誠一; 西尾和人 日本細胞生物学会大会(Web) 71st ROMBUNNO.1SDp‐04 (WEB ONLY) 2019年
• グライコアレイデータの探索型因子分析によるギラン・バレー症候群診断に関連する潜在因子の同定

  尾村誠一; 清水和秋; 桑原基; 森川みゆき; 藤田貢; 朴雅美; 佐藤文孝; PEDIO Erika; 楠進; 角田郁生 近畿大学医学雑誌 43 (3-4) 18A -18A 2018年12月
• 転写因子T‐bet過剰発現は神経向性ウイルス感染において致死的となる

  佐藤文孝; 川合英一郎; MARTINEZ Nicholas; 尾村誠一; 藤田貢; 朴雅美; 高橋智; 楊景堯; 角田郁生 Neuroinfection 23 (2) 208 -208 2018年10月
• 〈第76回近畿大学医学会学術講演会〉ウイルスによる自然発症自己免疫モデルの増悪

  佐藤 文孝; 尾村 誠一; 朴 雅美; 藤田 貢; 角田 郁生 近畿大学医学雑誌 = Medical Journal of Kindai University 42 (3) 25A2 -25A2 2017年12月
• 〈第76回近畿大学医学会学術講演会〉Rを用いた主成分分析による多発性硬化症マウスモデル病態・病理像関連バイオマーカーの同定

  尾村 誠一; 佐藤 文孝; Nicholas E.Martinez; 朴 雅美; 藤田 貢; Phillip; C.S.R.Kilgore; Urska Cvek; Marjan Trutschl; Alireza Minagar; J. Steven Alexander; 角田 郁生 近畿大学医学雑誌 = Medical Journal of Kindai University 42 (3) 26A2 -26A2 2017年12月
• 次世代シークエンシングを用いたウイルス性脳脊髄炎モデルの解析;リンパ管分子発現低下が免疫細胞の中枢神経内停滞に関連する

  尾村誠一; 佐藤文孝; 藤田貢; 朴雅美; STEVEN Alexander J; KILGORE Phillip; C. S. R; CVEK Urska; 角田郁生 Neuroinfection 22 (2) 218 -218 2017年09月
• タイラーウイルス誘導性脳脊髄炎モデルにおける制御性T細胞の役割

  佐藤 文孝; Martinez Nicholas; Karlsson Fridrik; 尾村 誠一; 朴 雅美; 藤田 貢; Grisham Matthew; 角田 郁生 Cytometry Research 27 (Suppl.) 54 -54 2017年06月
• 転写因子T‐bet過剰発現は神経向性ウイルス感染を増悪させる

  佐藤文孝; 川合英一郎; マルチネス ニコラス; 尾村誠一; 藤田貢; 朴雅美; 崎山奈美江; 高橋智; 楊景堯; 角田郁生 Neuroimmunology 22 (1) 112 -112 2017年
• 進行型多発性硬化症モデルでは血管接着分子の発現増加,BBB/リンパ管分子の発現減少が病因に相関する

  尾村誠一; 尾村誠一; 佐藤文孝; 佐藤文孝; ALEXANDER J. Steven; KILGORE Phillip; C. S. R; CVEK Urska; TRUTSCHL Marjan; 角田郁生; 角田郁生 Neuroimmunology 21 (1) 120 -120 2016年09月
• 感染因子による神経免疫疾患誘発のメカニズムと治療 ウイルス感染によって誘発される炎症性脱髄と軸索変性のメカニズム

  角田 郁生; 佐藤 文孝; 尾村 誠一; 崎山 奈美江; 朴 雅美; 藤田 貢 NEUROINFECTION 21 (2) 174 -174 2016年09月
• 進行型多発性硬化症モデルでは血管接着分子の発現増加、BBB/リンパ管分子の発現減少が病因に相関する

  尾村 誠一; 佐藤 文孝; Steven Alexander J; Kilgore Phillip C.S.R; Urska Cvek; Marjan Trutschl; 角田 郁生 神経免疫学 21 (1) 120 -120 2016年09月
• Role of CD4⁺ T cells in the pathophysiology of multiple sclerosis

  Fumitaka Sato; Seiichi Omura; S. L. Jaffe; Ikuo Tsunoda Multiple Sclerosis: A Mechanistic View 41 -69 2016年01月
• Animal Models of Multiple Sclerosis

  Fumitaka Sato; Seiichi Omura; Nicholas E. Martinez; Ikuo Tsunoda Neuroinflammation 55 -79 2011年12月
• Occupational health survey on workers handling titanium dioxide

  S. Ichihara; T. Kobayashi; S. Omura; W. Li; X. Ding; Y. Hiraku; Y. Hiraku; G. Ichihara TOXICOLOGY LETTERS 205 S284 -S284 2011年08月
• 再発寛解型および一次性進行型多発性硬化症動物モデルにおけるマイクロアレイを用いたシステム生物学的解析

  尾村誠一; 佐藤文孝; MARTINEZ Nicholas E; KENNETT Nikki J; ALEXANDER J. Steven; 角田郁生 日本神経免疫学会学術集会抄録集 23rd 67 -67 2011年
• 多発性硬化症ウイルスモデルにおけるTh17inducer,curdlan投与の影響

  佐藤文孝; MARTINEZ Nicholas E; 尾村誠一; ALEXANDER J. Steven; 角田郁生 日本神経免疫学会学術集会抄録集 23rd 80 -80 2011年
• 1G0954 ハイアイドル時ディーゼル排気短期曝露がラット心臓の遺伝子発現へ及ぼす影響の解析(3影響-1生体(疫学,毒性,癌・変異原性),一般研究発表)

  尾村 誠一; 藤谷 雄二; 小林 隆弘 大気環境学会年会講演要旨集 (50) 287 -287 2009年08月

受賞

• 2016年04月 The International Society for Neurovascular Disease The International Society for Neurovascular Disease’s Award for Best Abstract-Poster
   

  受賞者: 尾村誠一
• 2014年05月 日本神経学会 国際トラベルグラント
   

  受賞者: 尾村誠一
• 2013年07月 The American Society for Virology Medical Virology Club Travel Grant
   

  受賞者: 尾村誠一
• 2012年07月 The American Society for Virology Travel Award for Postdoctoral Fellow
   

  受賞者: 尾村誠一

共同研究・競争的資金等の研究課題

• ウイルス感染によって誘導される神経炎症における血小板の役割

  近畿大学：21世紀研究開発奨励金 【共同研究助成金】

  研究期間 : 2023年04月 -2026年03月 

  代表者 : 尾村誠一; 河原佐智代; 桑原基
• 多発性硬化症の発症・病態における IgA と腸内細菌の役割

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2022年04月 -2025年03月 

  代表者 : 尾村 誠一
• バイオインフォマティクスによるウイルス性心筋炎予後判定・治療に寄与する分子の同定

  日本学術振興会：科学研究費基盤研究(C)

  研究期間 : 2019年04月 -2022年03月 

  代表者 : 尾村誠一
• 宿主防御因子網羅的解析 データを用いたバイオインフォマティクス による ウイ ルス性心筋炎 予後判定・治療バイオマーカーの同定

  ノバルティスファーマ株式会社：ノバルティス研究助成

  研究期間 : 2019年04月 -2020年03月
• 多発性硬化症のウイルスモデルのTh17/Treg細胞の役割は病期によって異なるか

  日本学術振興会：科学研究費助成事業

  研究期間 : 2016年08月 -2018年03月 

  代表者 : 角田 郁生; 尾村 誠一

   

  従来、多発性硬化症(MS) では、IL-17 産生型ヘルパーT 細胞(Th17) は増悪に、制御性T 細胞(Tregs) は抑制に働くとされてきた。我々はMS のウイルスモデルであるタイラーウイルス誘導性脱髄疾患を用いてTh17 には1) 炎症の増悪、2) 抗ウイルス免疫の抑制、3) 神経保護作用の3 つの、またTregs には1) 炎症の抑制、2) 抗ウイルス免疫の抑制の2 つの善玉・悪玉双方の役割があることを解明した。これにより将来的にヒトMSの免疫調整治療には個々の症例のTh17・Tregsの役割に基づいて治療方針をたてるべきであることが示唆された。
• ウイルス性心筋炎モデルのトランスクリプトームビッグデータを用いた心筋炎診断バイオマーカー同定パイプラインの構築

  近畿大学：平成29年度近畿大学学内研究助成金奨励研究助成金

  研究期間 : 2017年04月 -2018年03月
• Systems biology approach for molecular mechanisms involved in viral myocarditis

  the Malcolm Feist Cardiovascular Research Endowment, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport.：Malcolm Feist Cardiovascular Fellowship

  研究期間 : 2012年08月 -2016年03月
• 工業的ナノ素材の心肺機能への影響に関する調査研究

  日本学術振興会：科学研究費助成事業

  研究期間 : 2008年 -2010年 

  代表者 : 市原 佐保子; 平工 雄介; 市原 学; 小林 隆弘; 尾村 誠一; 久永 直見; 柴田 英治

   

  中国の上海市にあるナノ酸化チタン取扱い工場に働く労働者を対象に、健康診断を実施し、労働現場の調査では、粒子数の計測をした。作業現場で労働者に装着したholter心電図の結果を解析し、粒子数や重量濃度と心拍数との関連を検討した結果、労働者によっては、ナノ粒子数と心拍数に有意な関連が認められた。また、粒子数計測の結果より、肉眼的埃っぽさは凝集体によるものと考えら、ナノ素材のヒトへの健康影響を考える上では、凝集体の影響も検討する必要があることが明らかになった。

担当経験のある科目

病原微生物学近畿大学医学部

その他

• 2017年04月 - 2017年04月  ウイルス性心筋炎モデルのトランスクリプトームビッグデータを用いた 心筋炎診断バイオマーカー同定パイプラインの構築 

  近畿大学学内研究助成金 奨励研究助成金 SR07 研究内容：RNA シークエンシング（RNA-seq）を用いて、ウイルス性心筋炎モデルの心筋からトランスクリプトームデータを得た。RNA-seq は新規の網羅的遺伝子発現解析手法であり、最適な“パイプライン”（コンピュータ処理工程）が未だ確立されていないため、本助成金により解析環境を整備し、バイオマーカー同定に最適なデータを得るためのパイプラインを構築した。

その他のリンク

researchmap

https://researchmap.jp/somura