中司 寛子 (ナカツカサ ヒロコ)

Nakatsukasa, Hiroko

写真a

所属(所属キャンパス)

医学部 微生物学・免疫学教室 (信濃町)

職名

助教(有期)

経歴 【 表示 / 非表示

  • 2011年04月
    -
    2014年05月

    National Institute of Dental and Craniofacial Research, NIH, Visiting Fellow

  • 2012年01月
    -
    2013年12月

    日本学術振興会海外特別研究員(NIH)

  • 2014年04月
    -
    2017年06月

    慶應義塾大学医学部, 微生物学免疫学教室, 特任助教

  • 2015年04月
    -
    2017年06月

    日本学術振興会特別研究員(PD)

  • 2017年07月
    -
    継続中

    慶應義塾大学医学部, 微生物学免疫学教室, 助教

学歴 【 表示 / 非表示

  • 2011年03月

    東京理科大学, 薬学研究科

    大学院, 修了, 博士後期

学位 【 表示 / 非表示

  • 博士(薬学), 東京理科大学, 課程, 2011年03月

免許・資格 【 表示 / 非表示

  • 薬剤師免許

 

研究分野 【 表示 / 非表示

  • 免疫学

 

論文 【 表示 / 非表示

  • Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery

    Ito M., Komai K., Mise-Omata S., Iizuka-Koga M., Noguchi Y., Kondo T., Sakai R., Matsuo K., Nakayama T., Yoshie O., Nakatsukasa H., Chikuma S., Shichita T., Yoshimura A.

    Nature (Nature)  565 ( 7738 ) 246 - 250 2019年01月

    ISSN  00280836

     概要を見る

    © 2019, Springer Nature Limited. In addition to maintaining immune tolerance, FOXP3 + regulatory T (T reg ) cells perform specialized functions in tissue homeostasis and remodelling 1,2 . However, the characteristics and functions of brain T reg cells are not well understood because there is a low number of T reg cells in the brain under normal conditions. Here we show that there is massive accumulation of T reg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain T reg cells are similar to T reg cells in other tissues such as visceral adipose tissue and muscle 3–5 , they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT 7 . The amplification of brain T reg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain T reg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that T reg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.

  • IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse

    Oike T., Kanagawa H., Sato Y., Kobayashi T., Nakatsukasa H., Miyamoto K., Nakamura S., Kaneko Y., Kobayashi S., Harato K., Yoshimura A., Iwakura Y., Takeuchi T., Matsumoto M., Nakamura M., Niki Y., Miyamoto T.

    Scientific Reports (Scientific Reports)  8 ( 1 )  2018年12月

     概要を見る

    © 2018, The Author(s). Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.

  • Inhibition of Nr4a receptors enhances antitumor immunity by breaking treg-mediated immune tolerance

    Hibino S., Chikuma S., Kondo T., Ito M., Nakatsukasa H., Omata-Mise S., Yoshimura A.

    Cancer Research (Cancer Research)  78 ( 11 ) 3027 - 3040 2018年06月

    ISSN  00085472

     概要を見る

    © 2018 American Association for Cancer Research. Enhanced infiltration of regulatory T cells (Treg) into tumor tissue is detrimental to patients with cancer and is closely associated with poor prognosis as they create an immunosuppressive state that suppresses antitumor immune responses. Therefore, breaking Treg-mediated immune tolerance is important when considering cancer immunotherapy. Here, we show that the Nr4a nuclear receptors, key transcription factors maintaining Treg genetic programs, contribute to Treg-mediated suppression of antitumor immunity in the tumor microenvironment. Mice lacking Nr4a1 and Nr4a2 genes specifically in Tregs showed resistance to tumor growth in transplantation models without exhibiting any severe systemic autoimmunity. The chemotherapeutic agent camptothecin and a common cyclooxygenase-2 inhibitor were found to inhibit transcriptional activity and induction of Nr4a factors, and they synergistically exerted antitumor effects. Genetic inactivation or pharmacologic inhibition of Nr4a factors unleashed effector activities of CD8þ cytotoxic T cells and evoked potent antitumor immune responses. These findings demonstrate that inactivation of Nr4a in Tregs breaks immune tolerance toward cancer, and pharmacologic modulation of Nr4a activity may be a novel cancer treatment strategy targeting the immunosuppressive tumor microenvironment. Significance: This study reveals the role of Nr4a transcription factors in Treg-mediated tolerance to antitumor immunity, with possible therapeutic implications for developing effective anticancer therapies

  • Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status

    Kanamori M., Nakatsukasa H., Ito M., Chikuma S., Yoshimura A.

    International Immunology (International Immunology)  30 ( 8 ) 357 - 373 2018年

    ISSN  09538178

     概要を見る

    © The Japanese Society for Immunology. 2018. T helper type 1 (Th1) cells form one of the most stable CD4 T-cell subsets, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here, we established a culture method for inducing Foxp3 from Th1 cells of mice and humans. This is achieved simply by resting Th1 cells without T-cell receptor ligation before stimulation in the presence of transforming growth factor-beta (TGF-ß). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo. Th1reg cells could also be induced from in vivo-developed mouse Th1 cells. Unexpectedly, the resting process enabled Foxp3 expression not through epigenetic changes at the locus, but through metabolic change resulting from reduced mammalian target of rapamycin complex 1 (mTORC1) activity. mTORC1 suppressed TGF-ß-induced phosphorylation of Smad2/3 in Th1 cells, which was restored in rested cells. Our study warrants future research aiming at development of immunotherapy with Th1reg cells.

  • D-mannose induces regulatory T cells and suppresses immunopathology

    Zhang, D., Chia, C., Jiao, X., Jin, W., Kasagi, S., Wu, R., Konkel, J. E., Nakatsukasa, H., Zanvit, P., Goldberg, N., Chen, Q., Sun, L., Chen, Z. J. and Chen, W.

    Nat Med 23 ( 9 ) 1036 - 1045 2017年09月

    ISSN  1546-170X

     概要を見る

    D-mannose, a C-2 epimer of glucose, exists naturally in many plants and fruits, and is found in human blood at concentrations less than one-fiftieth of that of glucose. However, although the roles of glucose in T cell metabolism, diabetes and obesity are well characterized, the function of D-mannose in T cell immune responses remains unknown. Here we show that supraphysiological levels of D-mannose safely achievable by drinking-water supplementation suppressed immunopathology in mouse models of autoimmune diabetes and airway inflammation, and increased the proportion of Foxp3+ regulatory T cells (Treg cells) in mice. In vitro, D-mannose stimulated Treg cell differentiation in human and mouse cells by promoting TGF-beta activation, which in turn was mediated by upregulation of integrin alphavbeta8 and reactive oxygen species generated by increased fatty acid oxidation. This previously unrecognized immunoregulatory function of D-mannose may have clinical applications for immunopathology.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • Treg/Th17細胞分化におけるDNA脱メチル化酵素TETの機能解明

    2020年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 中司 寛子, 基盤研究(C), 補助金,  代表

  • T細胞分化におけるDNA脱メチル化酵素TETの機能解明

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 中司 寛子, 若手研究, 補助金,  代表

  • 制御性T細胞のエピジェネティック制御機構の解明と免疫疾患への応用

    2015年04月
    -
    2017年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 中司 寛子, 若手研究(B), 補助金,  代表

     研究概要を見る

    制御性T細胞(Treg)は免疫寛容に重要なT細胞であり、その安定性はマスター遺伝子であるFoxp3のDNA脱メチル化が関与すると報告されたが、未だその制御機構には不明な点が多い。本研究では、DNA脱メチル化酵素であるTet2/3がT細胞およびTregにおいてDNA脱メチル化を制御することでその分化や安定性、機能に重要な役割を担うことを明らかとした。さらに、人工的にFoxp3遺伝子の部位特異的DNA脱メチル化を誘導することに成功した。

 

担当授業科目 【 表示 / 非表示

  • 免疫学

    2020年度

  • 免疫学

    2019年度