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末梢性自己寛容におけるサイトカインシグナルの働き

Research Project

Project/Area Number 20060032
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo University of Science (2009)
The Institute of Physical and Chemical Research (2008)

Principal Investigator

久保 允人  Tokyo University of Science, 生命科学研究所, 教授 (40277281)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2009: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2008: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsサイトカイン / Jak型チロシンキナーゼ / ヘルパーT細胞 / 制御性T細胞 / 自己免疫性疾患
Research Abstract

サイトカインに対する受容体は、細胞内ドメインに会合するJak型チロシンキナーゼと転写因子STATによって制御されている。感染症などによって引き起こされる急性炎症は、急激なサイトカイン産生を引き起こし、時として過剰な炎症反応などが伴うことによって免疫反応のバランスが破綻し、生体を死に至らしめる危険性すら生み出す。この危険性を回避するため、SOCS (Suppressor of Cytokine Signaling)は、Jak/STATシグナル伝達系を抑制することにより、サイトカインバランスの恒常性を厳格に制御するシグナル伝達分子として存在している。このSOCS分子の発現制御の破綻は、サイトカインバランスの変調を引き起こし、ヘルパーT細胞のバランスに破綻を誘導する。そこで本研究では末梢性自己寛容の維持の機構におけるSOCS1およびSOCS3分子の役割を明らかにするため、自己免疫性疾患を制御するサイトカインIL-17を産生するヘルパーT細胞、Th17と自己反応性を抑制的に制御するTGF-bによって誘導される制御性T細胞(Treg)の制御に焦点を当て研究を行った。SOCS1およびSOCS3の発現はIL-6によって誘導された。Th17の分化はT細胞特異的SOCS3欠損マウスで顕著に亢進し、Th17によって誘導される自己免疫性EAE反応も顕著に亢進したことから、SOCS3はT細胞上のIL-6の受容体に結合することで、そのシグナルを抑制することで、Th17分化を抑制する。一方、IL-6によって誘導されたSOCS1は、IL-2によって活性化されるSTAT5の活性化を抑制することで、制御性T細胞の分化を抑制的に制御していた。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (11 results)

All 2010 2009 2008

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (2 results)

  • [Journal Article] Lothar Hennighausen, Lionel Feigenbaum, and Alfred Singer : Signaling by intrathymic cytokines, not T cell receptors, specifies CD8-lineage choice and promotes differentiation of cytotoxic-lineage T cells2010

    • Author(s)
      Jung-Hyun Park, Stanley Adoro, Terry Guinter, Batu Erman, Amala Alag, Marta Catalfamo, Yongzhi Cui, Philip J.Lucas, Ronald E.Gress, Kubo, M
    • Journal Title

      Nature Immunology 11(3)

      Pages: 257-264

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Natural Occurring II-17 producing T cells regulate the initial phase of neutrophil mediated airway responses.2009

    • Author(s)
      Tanaka, S., Yoshimoto, T., Naka, T., Nakae S., Iwakura Y., Cua, D., Kubo, M.
    • Journal Title

      J.Immunol. 183(11)

      Pages: 7523-7530

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice2009

    • Author(s)
      Soichiro Fushimi ; Tetsuya Ogino ; Junko Hara ; Tomohiro Takahata ; Hiroshi Wakabayashi ; Haruyuki Watanabe ; Yasuharu Arashima, Kubo, M., Matsukawa, A.
    • Journal Title

      Clinical Immunol 133(3)

      Pages: 437-446

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary suppressor of cytokine signalling (SOCS)-1 induced by IL-13 as regulates allergic asthma2009

    • Author(s)
      Fukuyama, S., Nakano, T., Matsumoto, T., Oliver, B.G.G., Burgess, J., Moriwaki, A., Tanaka, K., Kubo, M., Hoshino, T., Tanaka, H., McKenzie, A.N.J.Matsumoto, K., Aizawa, H., Nakanishi, Y., Yoshimura, A., Black, J.L., Inoue, H
    • Journal Title

      Am.J.Respiratory and Critical Care Med. 179(11)

      Pages: 992-998

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MINA53, an 114 co-repressor controlling Th2-bias2009

    • Author(s)
      Okamoto, M., Van Stry, M., Chung, L., Koyanagi, M., Sun, X., Suzuki, Y., Ohara, O., Kitamura, H., Hijikata, A., Kubo, M.^* M., Bix
    • Journal Title

      Nature Immunology 10,8

      Pages: 872-879

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Th1 vs.Th17 differentiation : Selective contoribution of thetranscription factor IRF1 to the IFN-γ-IL-12 axis of signaling networks in CD4^+ T cells2008

    • Author(s)
      Kano, S., Sato, K., Morishita, Y., Vollstedt, S., Taki, S., Honda, K., Kubo, M., & Taniguchi, T.
    • Journal Title

      Nature Immunology 9(1)

      Pages: 34-41

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Murine IL-4 is able to signal via chimeric human IL-4Rα/mouse γ-chain receptor2008

    • Author(s)
      Myburgh, E., Horsnell, W., Cutler, A.J., Arendse, B., Kubo, M.,Brombacher, F.
    • Journal Title

      Molecular Immunology 45(5)

      Pages: 1327-1336

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pleiotropic Roles of Runx Transcription Factors in the Differentiation and Function of T Lymphocytes2008

    • Author(s)
      Kohfu, K.,Kubo, M., Ichikawa, H., Ohno, S., Habu, S., Sato, T., and Satake, M.
    • Journal Title

      Current Immunology Reviews 4

      Pages: 101-115

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BLNK suppresses pre-B cell leukemogenesis though inhibition of Jak32008

    • Author(s)
      Nakayama, J., Yamamoto, M., Hayashi, K., Satoh, H., Bundo, K., Kudo, M., Goitsuka, R., Farrar, M.A., Kitamura, D.
    • Journal Title

      Blood Dec.1

      Pages: 1483-1492

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Update on the National Genomic Projects for allergic diseases in Japan Japanese Society of Allergology, "Immuno-epigenetics of alleraic diseases"2009

    • Author(s)
      Masato Kubo
    • Organizer
      World Allergy Congress Argentina 2009
    • Place of Presentation
      Buenos Aires
    • Year and Date
      2009-12-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] Runx/CBF-β is a critical gatekeeper that directs the Th1 and Th17 differentiation2009

    • Author(s)
      Masato Kubo
    • Organizer
      International Workshop of Kyoto T cell Conference 2009
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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