加畑 宏樹 (カバタ ヒロキ)

Kabata, Hiroki

写真a

所属(所属キャンパス)

医学部 内科学教室(呼吸器) (信濃町)

職名

助教(有期)

その他の所属・職名 【 表示 / 非表示

  • 理化学研究所 生命医科学研究センター, 自然免疫システム研究チーム, 客員研究員

経歴 【 表示 / 非表示

  • 2006年04月
    -
    2008年03月

    独立行政法人国立病院機構東京医療センター, 初期研修医

  • 2008年04月
    -
    2009年03月

    慶應義塾大学医学部, 専修医

  • 2009年04月
    -
    2010年03月

    川崎市立川崎病院, 総合診療科, 専修医

  • 2011年05月
    -
    2014年03月

    慶應義塾大学医学部, 内科学, 助教(臨床実習)

  • 2014年04月
    -
    2016年04月

    川崎市立川崎病院, 呼吸器内科, 副医長

全件表示 >>

学歴 【 表示 / 非表示

  • 2000年04月
    -
    2006年03月

    慶應義塾, 医学部

    大学, 卒業

  • 2010年04月
    -
    2014年03月

    慶應義塾, 大学院, 医学研究科

    大学院, 卒業, 博士

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾, 論文, 2014年03月

    気道炎症の際にTSLPはナチュラルヘルパー細胞のステロイド抵抗性を誘導する

免許・資格 【 表示 / 非表示

  • 日本内科学会, 認定医, 2009年09月

  • 日本呼吸器学会, 専門医, 2013年12月

  • 日本アレルギー学会, 専門医, 2016年

 

研究分野 【 表示 / 非表示

  • 免疫学 (ILC2)

  • 呼吸器内科学 (喘息)

研究キーワード 【 表示 / 非表示

  • 2型自然リンパ球

  • IL-33

  • TSLP

  • 重症喘息

 

論文 【 表示 / 非表示

  • Neuro-immune crosstalk and allergic inflammation

    Kabata H., Artis D.

    Journal of Clinical Investigation (Journal of Clinical Investigation)  129 ( 4 ) 1475 - 1482 2019年04月

    査読有り,  ISSN  00219738

     概要を見る

    © 2019 American Society for Clinical Investigation. The neuronal and immune systems exhibit bidirectional interactions that play a critical role in tissue homeostasis, infection, and inflammation. Neuron-derived neuropeptides and neurotransmitters regulate immune cell functions, whereas inflammatory mediators produced by immune cells enhance neuronal activation. In recent years, accumulating evidence suggests that peripheral neurons and immune cells are colocalized and affect each other in local tissues. A variety of cytokines, inflammatory mediators, neuropeptides, and neurotransmitters appear to facilitate this crosstalk and positive-feedback loops between multiple types of immune cells and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems. In this Review, we discuss these recent findings regarding neuro-immune crosstalk that are uncovering molecular mechanisms that regulate inflammation. Finally, neuro-immune crosstalk has a key role in the pathophysiology of allergic diseases, and we present evidence indicating that neuro-immune interactions regulate asthma pathophysiology through both direct and indirect mechanisms.

  • Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2.

    Zhou L, Chu C, Teng F, Bessman NJ, Goc J, Santosa EK, Putzel GG, Kabata H, Kelsen JR, Baldassano RN, Shah MA, Sockolow RE, Vivier E, Eberl G, Smith KA, Sonnenberg GF

    Nature (Nature)  568 ( 7752 ) 405 - 409 2019年04月

    ISSN  0028-0836

     概要を見る

    © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract 1–4 . The protective effects of IL-2 involve the generation, maintenance and function of regulatory T (T reg ) cells 4–8 , and the use of low doses of IL-2 has emerged as a potential therapeutic strategy for patients with inflammatory bowel disease 9 . However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we show, in a mouse model, that IL-2 is acutely required to maintain T reg cells and immunological homeostasis throughout the gastrointestinal tract. Notably, lineage-specific deletion of IL-2 in T cells did not reduce T reg cells in the small intestine. Unbiased analyses revealed that, in the small intestine, group-3 innate lymphoid cells (ILC3s) are the dominant cellular source of IL-2, which is induced selectively by IL-1β. Macrophages in the small intestine produce IL-1β, and activation of this pathway involves MYD88- and NOD2-dependent sensing of the microbiota. Our loss-of-function studies show that ILC3-derived IL-2 is essential for maintaining T reg cells, immunological homeostasis and oral tolerance to dietary antigens in the small intestine. Furthermore, production of IL-2 by ILC3s was significantly reduced in the small intestine of patients with Crohn’s disease, and this correlated with lower frequencies of T reg cells. Our results reveal a previously unappreciated pathway in which a microbiota- and IL-1β-dependent axis promotes the production of IL-2 by ILC3s to orchestrate immune regulation in the intestine.

  • Influence of the Number Multiple Disease-Modifying Factors in Japanese Patients with Severe Asthma

    Watanabe R., Baba R., Kamatani T., Kuwae M., Okuzumi S., Tanosaki T., Matsusaka M., Mochimaru T., Kabata H., Ueda S., Suzuki Y., Asano K., Fukunaga K.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 199 2019年

    ISSN  1073-449X

  • Response to Fungal Dysbiosis by Gut-Resident CX3CR1 <sup>+</sup> Mononuclear Phagocytes Aggravates Allergic Airway Disease

    Li X., Leonardi I., Semon A., Doron I., Gao I., Putzel G., Kim Y., Kabata H., Artis D., Fiers W., Ramer-Tait A., Iliev I.

    Cell Host and Microbe (Cell Host and Microbe)  24 ( 6 ) 847 - 856.e4 2018年12月

    ISSN  19313128

     概要を見る

    © 2018 Elsevier Inc. How mycobiota influence immunity in gut distal sites is not well understood. Li et al. developed protocols for gut-targeted depletion of phagocytes and mycobiota-free mice to investigate the influence of fungi on gut-lung crosstalk. They reveal that intestinal phagocytes sense fungal dysbiosis and mediate gut-lung-directed immunity to aggravate allergic airway disease.

  • The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

    Kabata H., Moro K., Koyasu S.

    Immunological Reviews (Immunological Reviews)  286 ( 1 ) 37 - 52 2018年11月

    ISSN  01052896

     概要を見る

    © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+-NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+-NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2-related health problems.

全件表示 >>

総説・解説等 【 表示 / 非表示

  • Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2

    Zhou L., Chu C., Teng F., Bessman N., Goc J., Santosa E., Putzel G., Kabata H., Kelsen J., Baldassano R., Shah M., Sockolow R., Vivier E., Eberl G., Smith K., Sonnenberg G.

    Nature (Nature)  568 ( 7752 ) 405 - 409 2019年04月

    ISSN  00280836

     概要を見る

    © 2019, The Author(s), under exclusive licence to Springer Nature Limited. Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract 1–4 . The protective effects of IL-2 involve the generation, maintenance and function of regulatory T (T reg ) cells 4–8 , and the use of low doses of IL-2 has emerged as a potential therapeutic strategy for patients with inflammatory bowel disease 9 . However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we show, in a mouse model, that IL-2 is acutely required to maintain T reg cells and immunological homeostasis throughout the gastrointestinal tract. Notably, lineage-specific deletion of IL-2 in T cells did not reduce T reg cells in the small intestine. Unbiased analyses revealed that, in the small intestine, group-3 innate lymphoid cells (ILC3s) are the dominant cellular source of IL-2, which is induced selectively by IL-1β. Macrophages in the small intestine produce IL-1β, and activation of this pathway involves MYD88- and NOD2-dependent sensing of the microbiota. Our loss-of-function studies show that ILC3-derived IL-2 is essential for maintaining T reg cells, immunological homeostasis and oral tolerance to dietary antigens in the small intestine. Furthermore, production of IL-2 by ILC3s was significantly reduced in the small intestine of patients with Crohn’s disease, and this correlated with lower frequencies of T reg cells. Our results reveal a previously unappreciated pathway in which a microbiota- and IL-1β-dependent axis promotes the production of IL-2 by ILC3s to orchestrate immune regulation in the intestine.

  • 気管支喘息 病態生理 2型自然リンパ球(ILC2)を介した喘息病態に対する嫌酒薬Aの抑制機序の検討

    松坂 雅子, 加畑 宏樹, 加川 志津子, 持丸 貴生, 田野崎 貴絵, 奥隅 真一, 桑江 美聡, 渡辺 理沙, 上田 壮一郎, 茂呂 和世, 福永 興壱

    日本呼吸器学会誌 ((一社)日本呼吸器学会)  8 ( 増刊 ) 152 - 152 2019年03月

    ISSN  2186-5876

  • 【気管支喘息:研究と診療の最前線】自然免疫と喘息

    加畑 宏樹, 福永 興壱

    呼吸器内科 ((有)科学評論社)  34 ( 1 ) 16 - 21 2018年07月

    ISSN  1884-2887

  • 【咳嗽をめぐって】好酸球性炎症を伴う咳嗽とグループ2自然リンパ球(ILC2)

    加畑 宏樹

    アレルギー・免疫 ((株)医薬ジャーナル社)  25 ( 4 ) 494 - 500 2018年03月

    ISSN  1344-6932

     概要を見る

    <文献概要>慢性咳嗽のうち,好酸球性炎症を伴う咳嗽(咳喘息,アトピー咳嗽,非喘息性好酸球性気管支炎)が半数以上を占めている。従来,好酸球性炎症はTh2細胞から産生される2型サイトカイン(interleukin[IL]-4やIL-5,IL-13など)によって引き起こされると考えられていたが,最近ではグループ2自然リンパ球(ILC2)も好酸球性炎症に寄与していると考えられている。特に,ウイルス感染後の好酸球性炎症にはILC2が関与し,気道におけるIL-33やthymic stromal lymphopoietin(TSLP),interferon(IFN)などの産生量によって,ILC2を介した好酸球性炎症が慢性化することが示唆されている。

  • 日本人重症喘息患者における難治化因子数が病態コントロールに与える影響

    渡辺 理沙, 福永 興壱, 馬塲 里英, 鎌谷 高志, 桑江 美聡, 奥隅 真一, 田野崎 貴絵, 松坂 雅子, 持丸 貴生, 加畑 宏樹, 上田 壮一郎, 鈴木 雄介, 浅野 浩一郎, 別役 智子

    日本呼吸器学会誌 ((一社)日本呼吸器学会)  7 ( 増刊 ) 325 - 325 2018年03月

    ISSN  2186-5876

全件表示 >>

競争的資金等の研究課題 【 表示 / 非表示

  • ILC2をターゲットとした新規抑制化合物・天然物の同定

    2020年04月
    -
    2022年03月

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

 

担当授業科目 【 表示 / 非表示

  • 内科学(呼吸器)講義

    2020年度