詳細

中嶋　千紗 （ナカシマ　チサ）

  • 医学科　特任准教授
Last Updated :2024/04/25

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

    患者さんに寄り添った治療を心がけます。

研究者情報

学位

  • 博士（医学）（2014年07月 京都大学）

ホームページURL

J-Global ID

現在の研究分野（キーワード）

    患者さんに寄り添った治療を心がけます。

研究分野

  • ライフサイエンス / 皮膚科学

研究活動情報

論文

  • Kenji Usui; Chisa Nakashima; Sonoko Takahashi; Takaharu Okada; Yoshihiro Ishida; Saeko Nakajima; Akihiko Kitoh; Takashi Nomura; Teruki Dainichi; Tetsuya Honda; Rumi Katsumoto; Noriko Konishi; Mutsuyoshi Matsushita; Atsushi Otsuka; Kenji Kabashima
    Journal of Allergy and Clinical Immunology 2023年11月
  • Chisa Nakashima; Maiko Kato; Atsushi Otsuka
    The Journal of Dermatology 50 3 280 - 289 2023年01月 
    Abstract In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS‐CoV‐2 is the causative pathogen of coronavirus disease 2019 (COVID‐19). Although this new COVID‐19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID‐19 can be classified into seven categories: (i) chilblain‐like skin eruption (e.g., COVID toes), (ii) urticaria‐like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID‐19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune‐mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain‐like lesions and herpes zoster after COVID‐19 mRNA vaccination have been published. Various skin diseases associated with COVID‐19 and COVID‐19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID‐19 infection, although it was initially called COVID‐toe and considered a COVID‐19‐associated cutaneous eruption. In fact, some COVID‐19‐associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID‐19‐ or COVID‐19 vaccine‐associated skin reactions need to be elucidated and verification of causal relationships is required.
  • Chisa Nakashima; Hiromi Doi; Saeko Nakajima; Tomoji Mashimo; Toru Oga; Akemi Ishida-Yamamoto; Tetsuya Honda; Yoshihiro Ishida; Atsushi Otsuka; Kenji Kabashima
    Allergology international : official journal of the Japanese Society of Allergology 71 4 545 - 547 2022年05月
  • Izumi Kishimoto; Ni Ma; Riko Takimoto-Ito; Chisa Nakashima; Atsushi Otsuka; Andrew F Walls; Hideaki Tanizaki; Naotomo Kambe
    Frontiers in immunology 13 1014924 - 1014924 2022年 
    A decrease in the number of basophils in the peripheral blood, or basopenia, has been noted, reflecting the activity of chronic spontaneous urticaria (CSU). Infiltration of basophils into the skin has also been reported, but the mechanism of basopenia in CSU has not been clarified. The phenomenon of basopenia during the active phase of urticaria was confirmed, and basophil numbers increased following symptom improvement in 15 out of 17 patients treated with omalizumab and in 13 of 15 patients treated with antihistamines. Our examination by immunostaining also revealed basophil infiltration of the CSU lesions, as in previous reports, but since most of our patients were already taking oral steroids, it was not considered appropriate to examine the relationship between basophil numbers in tissue and peripheral blood. Then, we used mouse model of contact hypersensitivity with a single application of oxazolone, which is known to stimulate basophil infiltration, and investigated basophil counts in the skin, peripheral blood, and bone marrow. In this model, a decrease in peripheral blood basophil numbers was observed one day after challenge, but not after 2 days, reflecting supplementation from the bone marrow. Indeed, when cultured basophils expressing GFP were transplanted into the peripheral blood, GFP-positive basophil numbers in the peripheral blood remained low even after 2 days of challenge. Despite differences among species and models, these results suggest that one reason for the decrease of basophils in the peripheral blood in CSU may involve migration of circulating basophils into the skin.
  • Chisa Nakashima; Shigeto Yanagihara; Atsushi Otsuka
    Allergology international : official journal of the Japanese Society of Allergology 71 1 40 - 46 2022年01月 
    Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.
  • Yasuo Yamamoto; Atsushi Otsuka; Yoshihiro Ishida; Lai San Wong; Judith A Seidel; Yumi Nonomura; Chisa Nakashima; Saeko Nakajima; Akihiko Kitoh; Takashi Nomura; Teruki Dainichi; Tetsuya Honda; Wataru Amano; Noriko Konishi; Mikio Hayashi; Mutsuyoshi Matsushita; Kenji Kabashima
    The Journal of allergy and clinical immunology 148 3 858 - 866 2021年09月 
    BACKGROUND: Sensory nerves regulate cutaneous local inflammation indirectly through induction of pruritus and directly by acting on local immune cells. The underlying mechanisms for how sensory nerves influence cutaneous acquired immune responses remain to be clarified. OBJECTIVE: This study aimed to explore the effect of peripheral nerves on cutaneous immune cells in cutaneous acquired immune responses. METHODS: We analyzed contact hypersensitivity (CHS) responses as a murine model of delayed-type hypersensitivity in absence or presence of resiniferatoxin-induced sensory nerve denervation. We conducted ear thickness measurements, flow cytometric analyses, and mRNA expression analyses in CHS. RESULTS: CHS responses were attenuated in mice that were denervated during the sensitization phase of CHS. By screening neuropeptides, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA expression was decreased in the dorsal root ganglia after denervation. Administration of PACAP restored attenuated CHS response in resiniferatoxin-treated mice, and pharmacological inhibition of PACAP suppressed CHS. Flow cytometric analysis of skin-draining lymph nodes showed that cutaneous dendritic cell migration and maturation were reduced in both denervated mice and PACAP antagonist-treated mice. The expression of chemokine receptors CCR7 and CXCR4 of dendritic cell s was enhanced by addition of PACAP in vitro. CONCLUSION: These findings indicate that a neuropeptide PACAP promotes the development of CHS responses by inducing cutaneous dendritic cell functions during the sensitization phase.
  • C. Nakashima; Y. Ishida; Y. Kaku; E.H. Epstein; A. Otsuka; K. Kabashima
    British Journal of Dermatology 182 2 487 - 488 2020年02月 [査読有り]
  • Yasuo Yamamoto; Atsushi Otsuka; Chisa Nakashima; Yoshihiro Ishida; Tetsuya Honda; Gyohei Egawa; Wataru Amano; Kenji Usui; Yuji Hamada; Masashi Wada; Atsuo Tanimoto; Noriko Konishi; Mikio Hayashi; Mutsuyoshi Matsushita; Kenji Kabashima
    Journal of dermatological science 97 2 161 - 164 2020年02月
  • Chisa Nakashima; Yoshihiro Ishida; Akihiko Kitoh; Atsushi Otsuka; Kenji Kabashima
    Experimental dermatology 28 12 1405 - 1411 2019年12月 
    Mast cells, eosinophils and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils and basophils) and the nervous system is involved in the pathogenesis of neurogenic inflammation, pain and pruritus. Emerging evidence shows that these cells are the main source of pruritogens such as histamine, neuropeptides and cytokines, which are potential new therapeutic targets for drug development in chronic pruritus. For instance, many Th2 cytokines including interleukin (IL)-4, 13 and 31 have been recognized as some of the most promising targets for the treatment of chronic pruritus in AD. In this review, we highlight the link between these three immune cell subsets and peripheral nerves, with emphasis on the development of chronic pruritus such as AD. We present cytokines and receptors of these three immune cells and peripheral nerves, and discuss the therapeutic potential of targeting these neuro-immunological processes.
  • Natsuko Iga; Atsushi Otsuka; Masahiro Hirata; Tatsuki R Kataoka; Hiroyuki Irie; Chisa Nakashima; Shigeto Matsushita; Hiroshi Uchi; Yuki Yamamoto; Takeru Funakoshi; Yasuhiro Fujisawa; Koji Yoshino; Taku Fujimura; Hiroo Hata; Yoshihiro Ishida; Kenji Kabashima
    Cancer science 110 11 3434 - 3441 2019年11月 
    Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.
  • Iga N; Otsuka A; Yamamoto Y; Nakashima C; Honda T; Kitoh A; Nakajima S; Egawa G; Nomura T; Dainichi T; Matsushita S; Tanizaki H; Yamamoto Y; Funakoshi T; Fujisawa Y; Fujimura T; Hata H; Ishida Y; Kabashima K
    PloS one 14 1 e0211135  2019年 [査読有り]
     
    Cancer immunotherapy has highlighted the clinical relevance of enhancing anti-tumor response of CD8+ T cells in several cancer types. Little is known, however, about the involvement of the immune system in extramammary Paget's disease (EMPD). We examined the cytotoxicity and the effector functions of CD8+ T cells using paired samples of peripheral blood and tumors by flow cytometry. Expression levels of perforin, granzyme B, IFN-g, TNF-a, and IL-2 in CD8+ tumor-infiltrating lymphocytes (TILs) were significantly lower than those in CD8+ T cells of peripheral blood. Significantly higher expression of PD-1 was found in CD8+TILs than in CD8+ T cells of peripheral blood. A high number of CD8+ cells was significantly associated with poor overall survival (OS) adjusted with age, sex, and clinical stage (hazard ratio [HR] = 5.03, P = 0.045, 95% confidence interval [CI] 1.03-24.4). On the other hand, the number of PD-1+ cells was not associated with OS or disease-free survival (DFS). Moreover, we found that tumor cells produced immunosuppressive molecule indoleamine 2,3-dyoxygenae (IDO). In conclusion, CD8+ TILs displayed an exhausted phenotype in EMPD. IDO expression seemed more relevant in inducing CD8 exhaustion than PD-1 upregulation or PD-L1 expression by immune cells. Restoring the effector functions of CD8+ TILs could be an effective treatment strategy for advanced EMPD.
  • Ishida Y; Nakashima C; Kojima H; Tanaka H; Fujimura T; Matsushita S; Yamamoto Y; Yoshino K; Fujisawa Y; Otsuka A; Kabashima K
    Scientific reports 8 1 15962 - 15962 2018年10月 [査読有り]
     
    Immune checkpoint blockade (ICB) induces a remarkable response in patients with certain cancers. However, the response rate is not yet satisfactory. Biomarkers that help physicians identify patients who would benefit from ICB need to be developed. Killer immunoglobulin-like receptors (KIRs) are a class of receptors that are mainly expressed by natural killer cells. KIR genotypes have been shown to influence the outcomes of patients with neuroblastoma and hematopoietic malignancies. KIRs may thus influence the clinical outcomes of melanoma patients receiving nivolumab. We aimed to identify the KIR genotype, or KIR/KIR-ligand combinations, which influence the outcomes of melanoma patients receiving nivolumab. We genotyped 112 melanoma patients who were treated with nivolumab for KIR and human leukocyte antigen. The clinical records of the patients were analyzed to determine if they showed a response to nivolumab, and whether or not they experienced adverse events. Our analysis showed that no KIR gene was associated with a response to nivolumab. The KIR/KIR-ligand combination did not correlate with a response to nivolumab. KIR genes were not predictive of experiencing adverse events of grade 2 or greater. We conclude that the KIR genotype or KIR/KIR-ligand genotype do not show predictive value in melanoma patients receiving nivolumab.
  • Nakashima C; Otsuka A; Seidel JA; Kabashima K
    European journal of dermatology : EJD 28 4 563 - 564 2018年08月 [査読有り]
  • Nakashima C; Otsuka A; Kabashima K
    Journal of dermatological science 91 1 3 - 8 2018年07月 [査読有り]
  • Nakashima C; Otsuka A; Kabashima K
    Experimental dermatology 27 4 327 - 331 2018年04月 [査読有り]
  • Wong LS; Otsuka A; Tanizaki H; Nonomura Y; Nakashima C; Yamamoto Y; Yen YT; Rerknimitr P; Honda T; Kabashima K
    International journal of dermatology 57 3 299 - 305 2018年03月 [査読有り]
     
    BACKGROUND: Repetitive frictional trauma can be induced in daily and occupational activities, such as daily ablutions with washcloths. The influence of frictional trauma on the skin barrier function, especially in the perspective of the components of stratum corneum (SC), has not yet been studied in detail. Raman spectroscopy is a noninvasive optical technique based on inelastic light scattering that is capable of measuring several components in the skin. In this study, we used Raman spectroscopy to investigate the change in natural moisturizing factor (NMF) components in the SC following repetitive physical friction. METHODS: Six healthy volunteers, who were included in the study after obtaining an informed consent, performed repetitive washing with soap using nylon towels on the forearm twice a day for 2 weeks and used Raman spectroscopy to investigate the change in NMF components in the SC. RESULTS: Compared with the control, which was washed with soap at the same frequency on the opposite forearm, a significant increase in the transepidermal water loss (TEWL) and a decrease in NMF, serine, and total lactate, responsible for maintenance the SC hydration and structuring and maintaining the epidermal barrier function, in the SC were found. CONCLUSIONS: Increased TEWL and decreased NMF are considered as an etiology of atopic dermatitis (AD); therefore, our findings provide evidence that daily activities with repetitive frictional trauma may be related to the predisposition of AD.
  • Kabashima K; Nakashima C; Nonomura Y; Otsuka A; Cardamone C; Parente R; De Feo G; Triggiani M
    Immunological reviews 282 1 114 - 120 2018年03月 [査読有り]
  • Wong LS; Otsuka A; Yamamoto Y; Nonomura Y; Nakashima C; Kitayama N; Usui K; Honda T; Kabashima K
    Journal of dermatological science 89 2 207 - 209 2018年02月 [査読有り]
  • Ueharaguchi Y; Honda T; Kusuba N; Hanakawa S; Adachi A; Sawada Y; Otsuka A; Kitoh A; Dainichi T; Egawa G; Nakashima C; Nakajima S; Murata T; Ono S; Arita M; Narumiya S; Miyachi Y; Kabashima K
    Journal of Allergy and Clinical Immunology 142 2 680 - 683 Journal of Allergy and Clinical Immunology 2018年 [査読有り]
  • N. Kitayama; A. Otsuka; Y. Nonomura; C. Nakashima; T. Honda; K. Kabashima
    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY 31 10 E449 - E450 2017年10月
  • Chisa Nakashima; Atsushi Otsuka; Naomi Kitayama; Tetsuya Honda; Kenji Kabashima
    EUROPEAN JOURNAL OF DERMATOLOGY 27 5 552 - 553 2017年09月 [査読有り]
  • Rerknimitr P; Otsuka A; Nakashima C; Kabashima K
    Inflammation and regeneration 37 14  2017年 [査読有り]
  • Pawinee Rerknimitr; Hideaki Tanizaki; Yasuo Yamamoto; Wataru Amano; Saeko Nakajima; Chisa Nakashima; Yumi Nonomura; Jade Wititsuwannakul; Yoshiki Miyachi; Atsushi Otsuka; Kenji Kabashima
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 137 1 248 - 251 2017年01月 [査読有り]
  • Wong LS; Otsuka A; Yamamoto Y; Nonomura Y; Nakashima C; Honda T; Dainichi T; Kitoh A; Nakajima S; Hirakawa S; Miyachi Y; Kabashima K
    Journal of dermatological science 83 2 148 - 151 2016年08月 [査読有り]
  • Roman Huber; Barbara Meier; Atsushi Otsuka; Gabriele Fenini; Takashi Satoh; Samuel Gehrke; Daniel Widmer; Mitchell P. Levesque; Joanna Mangana; Katrin Kerl; Christoffer Gebhardt; Hiroko Fujii; Chisa Nakashima; Yumi Nonomura; Kenji Kabashima; Reinhard Dummer; Emmanuel Contassot; Lars E. French
    SCIENTIFIC REPORTS 6 29914  2016年07月 [査読有り]
     
    Hypoxia is a hallmark of cancer that is strongly associated with invasion, metastasis, resistance to therapy and poor clinical outcome. Tumour hypoxia affects immune responses and promotes the accumulation of macrophages in the tumour microenvironment. However, the signals linking tumour hypoxia to tumour-associated macrophage recruitment and tumour promotion are incompletely understood. Here we show that the damage-associated molecular pattern High-Mobility Group Box 1 protein (HMGB1) is released by melanoma tumour cells as a consequence of hypoxia and promotes M2-like tumour-associated macrophage accumulation and an IL-10 rich milieu within the tumour. Furthermore, we demonstrate that HMGB1 drives IL-10 production in M2-like macrophages by selectively signalling through the Receptor for Advanced Glycation End products ( RAGE). Finally, we show that HMGB1 has an important role in murine B16 melanoma growth and metastasis, whereas in humans its serum concentration is significantly increased in metastatic melanoma. Collectively, our findings identify a mechanism by which hypoxia affects tumour growth and metastasis in melanoma and depict HMGB1 as a potential therapeutic target.
  • Nonomura Y; Otsuka A; Nakashima C; Seidel JA; Kitoh A; Dainichi T; Nakajima S; Sawada Y; Matsushita S; Aoki M; Takenouchi T; Fujimura T; Hatta N; Koreeda S; Fukushima S; Honda T; Kabashima K
    Oncoimmunology 5 12 e1248327  2016年 [査読有り]
     
    Although nivolumab is associated with a significant improvement in overall survival and progression-free survival, only 20 to 40% of patients experience long-term benefit. It is therefore of great interest to identify a predictive marker of clinical benefit for nivolumab. To address this issue, the frequencies of CD4+ T cell subsets (Treg, Th1, Th2, Th9, Th17 and Th22), CD8+ T cells, and serum cytokine levels (IFNγ, IL-4, IL-9, IL-10, TGF-β) were assessed in 46 patients with melanoma. Eighteen patients responded to nivolumab, and the other 28 patients did not. An early increase in Th9 cell counts during the treatment with nivolumab was associated with an improved clinical response. Before the first nivolumab infusion, the responders displayed elevated serum concentrations of TGF-β compared to non-responders. Th9 induction by IL-4 and TGF-β was enhanced by PD-1/PD-L1 blockade in vitro. The role of IL-9 in disease progression was further assessed using a murine melanoma model. In vivo IL-9 blockade promoted melanoma progression in mice using an autochthonous mouse melanoma model, and the cytotoxic ability of murine melanoma-specific CD8+ T cells was enhanced in the presence of IL-9 in vitro. These findings suggest that Th9 cells, which produce IL-9, play an important role in the successful treatment of melanoma patients with nivolumab. Th9 cells therefore represent a valid biomarker to be further developed in the setting of anti-PD-1 therapy.
  • 中嶋 千紗
    J. Dermatol. Sci. 79 3 310 - 313 2015年09月 [査読有り]
  • Shimizuhira C; Otsuka A; Honda T; Kitoh A; Egawa G; Nakajima S; Nakashima C; Watarai H; Miyachi Y; Kabashima K
    The Journal of investigative dermatology 134 11 2709 - 2718 2014年11月 [査読有り]
     
    Contact hypersensitivity (CHS) has been widely used to study cutaneous immune responses, as a prototype of delayed-type hypersensitivity. Although natural killer T (NKT) cells have been assumed to have an important role in CHS, their role is controversial. Here, we report the role of NKT cells in the sensitization phase of CHS, by promoting the survival and maturation of dendritic cells (DCs) in the draining lymph nodes (LNs). The CHS response was attenuated with Cd1d1(-/-) and Traj18(-/-) BALB/c mice in which NKT cells were absent. In the draining LNs, the number of effector T cells and cytokine production were significantly reduced with NKT cell-deficient mice. NKT cells activated and colocalized with DCs in the draining LNs after sensitization. The number of migrated and mature DCs was reduced in NKT cell-deficient mice 72 hours after FITC application. In in vitro experiments, activated NKT cells enhanced bone marrow-derived DC (BMDC) survivability via tumor necrosis factor (TNF) production from BMDCs. In addition, TNF production from BMDCs was partially suppressed by the neutralizing anti-CD54 or CD154 antibodies. Our data demonstrate that DC-NKT interaction has a pivotal role in the sensitization phase of CHS.
  • Chisa Nakashima; Atsushi Otsuka; Akihiko Kitoh; Tetsuya Honda; Gyohei Egawa; Saeko Nakajima; Satoshi Nakamizo; Makoto Arita; Masato Kubo; Yoshiki Miyachi; Kenji Kabashima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 134 1 100 - + 2014年07月 [査読有り]
     
    Background: Although eosinophils have been detected in several human skin diseases in the vicinity of basophils, how eosinophils infiltrate the skin and the role of eosinophils in the development of skin inflammation have yet to be examined. Objective: Using murine irritant contact dermatitis (ICD) as a model, we sought to clarify the roles of eosinophils in ICD and the underlying mechanism of eosinophil infiltration of the skin. Methods: We induced croton oil-induced ICD in eosinophil-deficient Delta dblGATA mice with or without a reactive oxygen species (ROS) inhibitor. We performed cocultivation with fibroblasts and bone marrow-derived basophils and evaluated eosinophil migration using a chemotaxis assay. Results: ICD responses were significantly attenuated in the absence of eosinophils or by treatment with the ROS inhibitor. ROS was produced abundantly by eosinophils, and both basophils and eosinophils were detected in human and murine ICD skin lesions. In coculture experiments, basophils attracted eosinophils, especially in the presence of fibroblasts. Moreover, basophils produced IL-4 and TNF-alpha in contact with fibroblasts and promoted the expression of eotaxin/CCL11 from fibroblasts in vitro. Conclusion: Eosinophils mediated the development of murine ICD, possibly through ROS production. Recruitment of eosinophils into the skin was induced by basophils in cooperation with fibroblasts. Our findings introduce the novel concept that basophils promote the recruitment of eosinophils into the skin through fibroblasts in the development of skin inflammation.
  • Nakashima C; Tanizaki H; Otsuka A; Miyachi Y; Kabashima K
    Dermatology online journal 20 6 2014年06月 [査読有り]
  • Combination therapy with a newly developed excimer lamp and topical steroids successfully treated intractable prurigo nodularis.
    中嶋 千紗
    Dermatol. Online J. 15 20 6  2014年06月 [査読有り]
  • A. Otsuka; H. Doi; G. Egawa; A. Maekawa; T. Fujita; S. Nakamizo; C. Nakashima; S. Nakajima; T. Watanabe; Y. Miyachi; S. Narumiya; K. Kabashima
    Journal of Allergy and Clinical Immunology 133 1 139-146.e10  2014年 [査読有り]
  • Chisa Nakashima; Atsushi Otsuka; Hiroko Sonobe; Akihiko Kitoh; Mayumi Kato; Satoshi Kore-Eda; Yoshiki Miyachi; Kenji Kabashima
    EUROPEAN JOURNAL OF DERMATOLOGY 22 5 693 - 693 2012年09月 [査読有り]
  • Mami Sato; Yumi Matsumura; Ayako Kojima; Chisa Nakashima; Mayumi Katoh; Satoshi Kore-Eda; Yoshiki Miyachi
    JOURNAL OF DERMATOLOGY 38 10 1037 - 1040 2011年10月 [査読有り]
  • 中嶋 千紗; 松村 由美; 高折 晃史; 宮地 良樹
    皮膚科の臨床 53 9 1265 - 1268 金原出版(株) 2011年09月 
    64歳女。52歳時に真性多血症と診断され、ヒドロキシカルバミドの投与を受けていた。左乳癌に対し乳房切除術を施行されたところ、翌日より両下肢が腫脹し、右第2、3、4趾先端に点状紫斑と疼痛を生じた。半年後より疼痛が著明となり、真性多血症に伴う末梢循環不全の診断でベラプロストナトリウムおよび塩酸サルポグレラートの内服が開始されたが、疼痛は増悪し、壊死が進行して術後10ヵ月目に当科初診となった。スルファジアジン銀クリーム外用を開始し、初診2ヵ月後に右第2〜4趾、8ヵ月後に第1趾の切断術を施行した。疼痛の訴えでヒドロキシカルバミドをいったん中止したが、両足の暗紫色変化、切断部の壊死拡大を来たし、真性多血症は増悪して潰瘍形成も認めた。同意を得てヒドロキシカルバミドを再開し、ワルファリンカリウムを開始したところ、暗紫色変化は次第に軽快し、切断部も上皮化して27ヵ月後に治癒した。臨床経過などより、真性多血症によるblue toe症候群と診断した。
  • ステロイド外用やプロトピック外用により悪化した酒さの1例
    長岡 悠美; 松村 由美; 楠葉 展大; 中嶋 千紗; 宮地 良樹
    皮膚の科学 9 3 299 - 299 日本皮膚科学会-大阪地方会・京滋地方会 2010年06月
  • 7年来服用していたフルバスタチンが原因と判明した環状を呈する紅斑の1例
    辻花 光次郎; 松村 由美; 中嶋 千紗; 加藤 真弓; 是枝 哲; 宮地 良樹; 十一 英子
    日本臨床皮膚科医会雑誌 27 2 266 - 266 日本臨床皮膚科医会 2010年04月
  • 摂食障害に伴う紅斑の2例
    佐藤 真美; 松村 由美; 小嶌 綾子; 中嶋 千紗; 加藤 真弓; 是枝 哲; 宮地 良樹
    皮膚の科学 9 2 188 - 188 日本皮膚科学会-大阪地方会・京滋地方会 2010年04月
  • 辻花 光次郎; 松村 由美; 中嶋 千沙; 加藤 真弓; 是枝 哲; 宮地 良樹; 十一 英子
    皮膚の科学 9 6 526 - 531 日本皮膚科学会大阪地方会・日本皮膚科学会京滋地方会 2010年 
    78歳，男性。5年前に発熱，呼吸困難を伴う肺炎，痒みを伴う皮疹を生じ，ステロイド内服を開始した。以後ステロイド減量により紅斑を再燃する経過を繰り返し，そのために5年来ステロイドを服用していた。悪性腫瘍の合併は認めなかった。前医でも薬疹が疑われたが患者の申告では内服薬はないとのことであり，皮疹の精査を目的に当科に紹介された。当院受診後，フルバスタチンがかかりつけ医で処方されていた事が判明した。処方した医師に問い合せ，7年前からの処方が判明した。フルバスタチン中止後，皮疹は2週間以内に消失し，以後9ヶ月間再燃はない。しかし，CT 上間質性肺炎の所見は残存している。フルバスタチンにより誘発された薬疹と肺炎と考えた。薬剤内服後2年後の発症であった点，再燃時にもステロイド内服中止から再発までしばらくの期間を要する点からアレルギー性の薬疹にしては非典型的である。(皮膚の科学，9: 526-531, 2010)
  • 中嶋 千紗
    Clinical and Experimental Dermatology. 33 4 437 - 439 2008年07月 [査読有り]
     
    Infliximab is a tumour necrosis factor (TNF)-alpha blocking drug classified as a biological response modifier. It has been suggested that the risk of malignancies, especially lymphomas, is increased in patients with rheumatoid arthritis (RA) treated with anti-TNF-alpha antibody therapy. We present a case of malignant lymphoma during the treatment of RA with infliximab and methotrexate.

MISC

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2022年04月 -2024年03月 
    代表者 : 中嶋 千紗
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 中嶋 千紗
     
    皮膚アレルギー疾患、例えばアトピー性皮膚炎患者の多くはかゆみを有しているが、そのメカニズムの詳細についてはまだ不明な部分が多い。また近年の報告で、アトピー性皮膚炎患者では、症状の増悪時に皮膚常在細菌叢の菌の種類が著しく減少し、黄色ブドウ球菌が過半数を占めると報告されている。そこで、我々は黄色ブドウ球菌の死菌をマウス耳介に塗布し慢性皮膚炎を誘発し、皮膚末梢神経と免疫細胞の役割について検証した。その中で、皮膚末梢神経と好塩基球が協調して黄色ブドウ球菌誘発皮膚炎の形成に寄与していることが分かった。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2014年08月 -2016年03月 
    代表者 : 中嶋 千紗
     
    掻痒は生活の質を低下させる身体症状の一つである。特に既存の治療では効果が不十分な事から新規治療法の開発は緊要の課題である。 これまでにアトピー性皮膚炎（AD）患者や乾皮症患者では多数の知覚神経線維が表皮内に侵入し、増生する。そこで我々は、皮膚透明化（CUBIC）の手法を用い、様々なマウスアレルギー性皮膚炎モデルにおける皮膚内の末梢神経の動態を観察した。イミキモド誘発乾癬様皮膚炎モデルにおいても、病変部の表皮内に神経線維の増生を認めた。また、VEGF-Aが表皮内神経線維の増生を促し、乾癬モデルマウスにおける掻痒の病態形成に関与している可能性が示唆された。

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