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2008 Fiscal Year Annual Research Report

インターロイキン17/17Fによる細菌感染防御機構の解析

Research Project

Project/Area Number 19041025
Research InstitutionThe University of Tokyo

Principal Investigator

岩倉 洋一郎  The University of Tokyo, 医科学研究所, 教授 (10089120)

Co-Investigator(Kenkyū-buntansha) 角田 茂  東京大学, 医科学研究所, 助教 (80345032)
西城 忍  東京大学, 医科学研究所, 助教 (60396877)
Keywordsサイトカイン / 細菌感染 / 自然免疫 / 獲得免疫 / 遺伝子改変マウス
Research Abstract

獲得免疫による細菌感染防御にはTh1応答が重要であると考えられてきたが、近年、細菌感染におけるTh17応答の役割が注目されている。IL-17は活性化T細胞が産生する炎症性サイトカインであり、好中球の遊走、炎症性メディエーターの発現誘導などを介して炎症性疾患の発症や生体防御に関与していると考えられている。また、IL-17のファミリー分子・IL-17FはTh17から産生され、IL-17とレセプターを共有し、生理活性も類似していると考えられているが、免疫系や感染防御に於ける両者の生理機能や役割分担には不明の部分が多い。本研究では、IL-17KO、IL-17FKO、IL-17/IL-17FKOマウスを用いて、細菌感染に対する自然免疫や獲得免疫の成立過程に於けるIL-17,およびIL-17Fの役割を細胞外寄生グラム陰性細菌(C. rodentium)、細胞外寄生グラム陽性細菌(S. aureus)をモデルとして検討した。C. rodentium感染においては、IL-17KO、IL-17FKOマウスの両方で感染が増悪化した。腸管上皮においては、IL-17/IL-17Fそれぞれがβディフェンシンの発現制御に関与しており、大腸菌感染防御を担っていることが明らかになった。一方、S. aureus感染においてはIL-17/IL-17FKOマウスのみが感染抵抗性が低下しており、腸管とは異なり鼻粘膜においてはIL-17とIL-17Fは重複した機能を持つことがわかった。IL-17/IL-17Fの発現細胞および受容体IL-17RA/IL-17RCの発現分布を詳細に検討した結果、これらは大きく異なっていた。このことが臓器特異性や病原菌特異性を示す一因と考えられた。

  • Research Products

    (20 results)

All 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] IFN-γ expression in CD8+T cells regulated by IL-6 signal is involved insuperantigen-mediated CD4+ T cell death2009

    • Author(s)
      Atsumi, T.
    • Journal Title

      Int. Immunol. 21

      Pages: 73-80

    • Peer Reviewed
  • [Journal Article] Characterization of mice deficient in Melanocortin 2 receptor on a B6/Balbc mixbackground2009

    • Author(s)
      Chida, D.
    • Journal Title

      Mol. Cell. Endocrinol. 300

      Pages: 32-36

    • Peer Reviewed
  • [Journal Article] Differential roles of IL-17A and IL-17F in host defense against mucoepithelial bacterial infection and allergic responses2009

    • Author(s)
      Ishigame, H.
    • Journal Title

      Immunity 29

      Pages: 628-636

    • Peer Reviewed
  • [Journal Article] Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9Dependent Pathway2008

    • Author(s)
      Nakamura, K.
    • Journal Title

      J. Immunol. 180

      Pages: 6067-4074

    • Peer Reviewed
  • [Journal Article] IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia2008

    • Author(s)
      Aujla, S.J.
    • Journal Title

      Nat. Med. 14

      Pages: 275-281

    • Peer Reviewed
  • [Journal Article] Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis2008

    • Author(s)
      Izcue, A.
    • Journal Title

      Immunity 28

      Pages: 559-570

    • Peer Reviewed
  • [Journal Article] Host T Cells Are the Main Producers of IL-17 within the Central Nervous System during Initiation of Experimental Autoimmune Encephalomyelitis Induced by Adoptive Transfer of Thl Cell Lines2008

    • Author(s)
      Lees, J.R.
    • Journal Title

      J. Immunol. 180

      Pages: 8066-8072

    • Peer Reviewed
  • [Journal Article] Increased fat : carbohydrate oxidation ratio in lllra^<-/-> mice on a high fat diet is associated with increased sympathetic tone2008

    • Author(s)
      Chida, D.
    • Journal Title

      Diabetologia 51

      Pages: 1698-1706

    • Peer Reviewed
  • [Journal Article] IL-17A is produced by Th17, γδT cells and other CD4-lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance2008

    • Author(s)
      Schulz, S.M.
    • Journal Title

      Int. Immunol. 20

      Pages: 1129-1138

    • Peer Reviewed
  • [Journal Article] Contribution of IL-1 to resistance to Streptococcus pneumoniae infection2008

    • Author(s)
      Kafka, D.
    • Journal Title

      Int. Immunol. 20

      Pages: 1139-1146

    • Peer Reviewed
  • [Journal Article] IL-17A Produced by γδT Cells Plays a Critical Role in Innate Immunity against Listeria monocytogenes Infection in the Liver2008

    • Author(s)
      Hamada, S.
    • Journal Title

      J. Immunol. 181

      Pages: 3456-3463

    • Peer Reviewed
  • [Journal Article] Human T-cell leukemia virus type I infects human lung epithelial cells and induces gene expression of cytokines, chemokines and cell adhesion molecules2008

    • Author(s)
      Teruya, H.
    • Journal Title

      Retrovirology 5

      Pages: 86

    • Peer Reviewed
  • [Journal Article] Toll-like receptor 2 (TLR2) and dectin-1 contribute to the production of IL-12p40 by bone marrow-derived dendritic cells infected with Penicillium marneffei2008

    • Author(s)
      Nakamura, K.
    • Journal Title

      Microbes Infect 10

      Pages: 1223-1227

    • Peer Reviewed
  • [Journal Article] Involvement of IL-17A in the pathogenesis of DSSinduced colitis in mice2008

    • Author(s)
      Ito, R.
    • Journal Title

      Biochem. Biophys.Res. Commun. 377

      Pages: 12-16

    • Peer Reviewed
  • [Journal Article] Protective Immunity to Systemic Infection with Attenuated Salmonella enterica serovar Enteritidis in the Absence of IL-12 Is Associated with IL-23-Dependent IL-22, but Not IL-172008

    • Author(s)
      Schulz, S.M.
    • Journal Title

      J. Immunol. 181

      Pages: 7891-7901

    • Peer Reviewed
  • [Journal Article] IL-17 is Involved in Helicobacter pylori-Induced Gastric Inflammatory Responses in a Mouse Model2008

    • Author(s)
      Shiomi, S.
    • Journal Title

      Helicobacter 13

      Pages: 518-524

    • Peer Reviewed
  • [Journal Article] The roles of IL-17A in inflammatory immune responses and host defense against pathogens2008

    • Author(s)
      Iwakura, Y.
    • Journal Title

      Immunol. Rev. 226

      Pages: 57-79

    • Peer Reviewed
  • [Presentation] A C-type lectin that involved in the host defense against fungi plays an important role in the development of autoimmune arthritis2008

    • Author(s)
      Shinobu Saijo
    • Organizer
      13th congress of the asia pacific league of associations for rheumatology
    • Place of Presentation
      Yokohama
    • Year and Date
      20080923-27
  • [Presentation] Differential roles of IL-17A and IL-17F in allergic responses and host defense against mucoepithelial bacterial infection2008

    • Author(s)
      Harumichi Ishigame
    • Organizer
      The 8th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Hyogo
    • Year and Date
      20080907-11
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/cem_dcb/index.html

URL: 

Published: 2010-06-11   Modified: 2016-04-21  

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