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2007 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 / 生体防御 / Th17 / 細菌感染 / 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-17 KO、IL-17F KO、IL-17/IL-17F KO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-17 KO、IL-17F KOマウスの両方で感染が増悪化し、IL-17、IL-17Fそれぞれが腸管における細菌感染防御において異なる機能を持つことが明らかになった。一方、S.aureus感染においてはIL-17/IL-17F KO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/IL-17Fは重複した機能を持つことがわかった。このような臓器特異性や病原菌特異性を示す原因は未だ不明であり、今後、その分子機構を詳細に検討する必要があると考えられた。

  • Research Products

    (41 results)

All 2008 2007 Other

All Journal Article (31 results) (of which Peer Reviewed: 31 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis.2008

    • Author(s)
      Izcue A.
    • Journal Title

      Immunity 28

      Pages: 559-570

    • Peer Reviewed
  • [Journal Article] Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category.2008

    • Author(s)
      Luger D.
    • Journal Title

      J Exp Med 205

      Pages: 799-810

    • Peer Reviewed
  • [Journal Article] Kid-mediated chromosome compaction ensures proper nuclear envelope formation.2008

    • Author(s)
      Ohsugi M.
    • Journal Title

      Cell 132

      Pages: 771-782

    • Peer Reviewed
  • [Journal Article] Deoxynucleic Acids from Cryptococcus neoformans Activate Myeloid Dendritic Cells via a TLR9-Dependent Pathway.2008

    • Author(s)
      Nakamura K.
    • Journal Title

      J Immunol 180

      Pages: 4067-4074

    • Peer Reviewed
  • [Journal Article] IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.2008

    • Author(s)
      Aujla SJ.
    • Journal Title

      Nat Med 14

      Pages: 275-281

    • Peer Reviewed
  • [Journal Article] Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17.2008

    • Author(s)
      Pichavant M.
    • Journal Title

      J Exp Med 205

      Pages: 385-393

    • Peer Reviewed
  • [Journal Article] Suppressive role of leukocyte cell-derived chemotaxin 2 in mouse anti-type II collagen antibody-induced arthritis.2008

    • Author(s)
      Okamura A.
    • Journal Title

      Arthritis Rheum 58

      Pages: 413-421

    • Peer Reviewed
  • [Journal Article] Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells.2008

    • Author(s)
      Fujikado N.
    • Journal Title

      Nat Med 14

      Pages: 176-180

    • Peer Reviewed
  • [Journal Article] Differential roles for IFN-γ and IL-17 in experimental autoimmune uveoretinitis.2008

    • Author(s)
      Yoshimura T.
    • Journal Title

      Int Immunol 20

      Pages: 209-214

    • Peer Reviewed
  • [Journal Article] Interleukin-1β and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression.2008

    • Author(s)
      Honda A.
    • Journal Title

      J Dermal Sci 49

      Pages: 63-72

    • Peer Reviewed
  • [Journal Article] Negative feedback regulation of lipopolysaccharide-induced inducible nitricoxide synthase gene expression by heme oxygenase-1 induction in macrophages.2008

    • Author(s)
      Ashino T.
    • Journal Title

      Mol Immunol 45

      Pages: 2106-2115

    • Peer Reviewed
  • [Journal Article] Dectin-1 is not required for the host defense to Cryptococcus neoformans.2007

    • Author(s)
      Nakamura K.
    • Journal Title

      Microbiol Immunol 51

      Pages: 1115-1119

    • Peer Reviewed
  • [Journal Article] Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis.2007

    • Author(s)
      Chida D.
    • Journal Title

      Proc Natl Acad Sci U S A 104

      Pages: 18205-18210

    • Peer Reviewed
  • [Journal Article] Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo.2007

    • Author(s)
      Miller LS.
    • Journal Title

      J Immunol 179

      Pages: 6933-6942

    • Peer Reviewed
  • [Journal Article] Blocking of IL-6 signaling pathway prevents CD4+ T cell-mediated colitis in a T_h17-independent manner.2007

    • Author(s)
      Noguchi D.
    • Journal Title

      Int Immunol 19

      Pages: 1431-1440

    • Peer Reviewed
  • [Journal Article] Peripheral TNFα, but not peripheral IL-1, requires endogenous IL-1 or TNFα induction in the brain for the febrile response.2007

    • Author(s)
      Chida D.
    • Journal Title

      Biochem Biophys Res Commun 364

      Pages: 765-770

    • Peer Reviewed
  • [Journal Article] Anti-type II collagen antibody accelerates arthritis via CXCR2-expressing cells in IL-1 receptor antagonist-deficient mice.2007

    • Author(s)
      Kagari T.
    • Journal Title

      Eur J Immunol 37

      Pages: 2269-2278

    • Peer Reviewed
  • [Journal Article] IL-23 enhances host defense against vaccinia virus infection via a mechanism partly involving IL-17.2007

    • Author(s)
      Kohyama S.
    • Journal Title

      J Immunol 179

      Pages: 3917-3925

    • Peer Reviewed
  • [Journal Article] Systemic administration of IL-23 induces potent antitumor immunity primarily mediated through Th1-type response in association with the endogenously expressed IL-12.2007

    • Author(s)
      Kaiga T.
    • Journal Title

      J Immunol 178

      Pages: 7571-7580

    • Peer Reviewed
  • [Journal Article] Interleukin-1 is not essential for expression of inducible NOS in hepatocytes induced by lipopolysaccharide in vivo.2007

    • Author(s)
      Takagi K.
    • Journal Title

      Nitric Oxide 16

      Pages: 433-441

    • Peer Reviewed
  • [Journal Article] IFN-γ protects cerulein-induced acute pancreatitis by repressing NF-κBactivation.2007

    • Author(s)
      Hayashi T.
    • Journal Title

      J Immunol 178

      Pages: 7385-7394

    • Peer Reviewed
  • [Journal Article] The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors.2007

    • Author(s)
      Hara H.
    • Journal Title

      Nat Immunol 8

      Pages: 619-629

    • Peer Reviewed
  • [Journal Article] Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses.2007

    • Author(s)
      Venkataraman T.
    • Journal Title

      J Immunol 178

      Pages: 6444-6455

    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase.2007

    • Author(s)
      Sato N.
    • Journal Title

      Clin Exp Allergy 37

      Pages: 743-751

    • Peer Reviewed
  • [Journal Article] IL-28 elicits antitumor responses against murine fibrosarcoma.2007

    • Author(s)
      Numasaki M.
    • Journal Title

      J Immunol 178

      Pages: 5086-5098

    • Peer Reviewed
  • [Journal Article] A new murine model to define the critical pathologic and therapeutic mediators of polymyositis.2007

    • Author(s)
      Sugihara T.
    • Journal Title

      Arthritis Rheum 56

      Pages: 1304-1314

    • Peer Reviewed
  • [Journal Article] Natural killer T cells from interleukin-4-deficient mice are defective in early interferon-γ production in response to α-galactosylceramide.2007

    • Author(s)
      Togashi Y.
    • Journal Title

      Cancer Sci 98

      Pages: 721-725

    • Peer Reviewed
  • [Journal Article] IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection.2007

    • Author(s)
      Umemura M.
    • Journal Title

      J Immunol 178

      Pages: 3786-3796

    • Peer Reviewed
  • [Journal Article] Role of interferon-γ in Vα14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungs.2007

    • Author(s)
      Nakamatsu M.
    • Journal Title

      Microbes Infect 9

      Pages: 364-374

    • Peer Reviewed
  • [Journal Article] Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17.2007

    • Author(s)
      Nakae S.
    • Journal Title

      J Leukocyte Biol 81

      Pages: 1258-1268

    • Peer Reviewed
  • [Journal Article] Intestinal inflammation downregulates smooth muscle CPI-17 through induction of TNF-α and causes motility disorders.2007

    • Author(s)
      Ohama T.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 292

      Pages: 1429-1438

    • Peer Reviewed
  • [Presentation] The roles of C-type lectins in the host defense against infection and homeostasis of the immune system2007

    • Author(s)
      Yoichiro Iwakura
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      品川
    • Year and Date
      20071120-22
  • [Presentation] Differential requirement of IL-17A and IL-17F in inflammatory responses and hostdefense against bacteria2007

    • Author(s)
      Harumichi Ishigame
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      品川
    • Year and Date
      20071120-22
  • [Presentation] Dectin-1の生体防御機構における役割2007

    • Author(s)
      西城忍
    • Organizer
      第51回日本医真菌学会総会
    • Place of Presentation
      高山
    • Year and Date
      20071109-10
  • [Presentation] The roles of interleukin (IL)-17A and IL-17F in the development of inflammatory responses.2007

    • Author(s)
      Harumichi Ishigame
    • Organizer
      The 15th Annual Meeting of the Intemational Cytokine Society
    • Place of Presentation
      San Francisco
    • Year and Date
      20071026-30
  • [Presentation] The roles of interleukin (IL)-17A and IL-17F in the development of inflammator\ responses.2007

    • Author(s)
      Harumichi Ishigame
    • Organizer
      The 13th International Congress of Immunology
    • Place of Presentation
      Rio de Janeiro
    • Year and Date
      20070821-25
  • [Presentation] Dectin-1 plays an important role in host defense against the pathogenic fungu Pneumocystis carinii.2007

    • Author(s)
      Shinobu Saijo
    • Organizer
      The 13th International Congress of Immunology
    • Place of Presentation
      Rio de Janeiro
    • Year and Date
      20070821-25
  • [Presentation] 炎症および感染防御におけるIL-17AとIL-17Fの役割2007

    • Author(s)
      石亀晴道
    • Organizer
      第72回日本インターフェロン・サイトカイン学会
    • Place of Presentation
      京都
    • Year and Date
      20070705-06
  • [Presentation] C型レクチンレセプターDCIRの関節炎発症における役割2007

    • Author(s)
      藤門範行
    • Organizer
      第72回日本インターフェロン・サイトカイン学会
    • Place of Presentation
      京都
    • Year and Date
      20070705-06
  • [Presentation] Dectin-1の生体防御機構における役割2007

    • Author(s)
      西城忍
    • Organizer
      第54回日本実験動物学会総会
    • Place of Presentation
      江戸川
    • Year and Date
      20070523-25
  • [Remarks]

    • URL

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

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Published: 2010-02-04   Modified: 2016-04-21  

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