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粘膜免疫監視の場としてのGALT・NALTを介した免疫制御誘導の解明

Research Project

Project/Area Number 17047009
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

清野 宏  東京大学, 医科学研究所, 教授 (10271032)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2006: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywords鼻咽腔関連リンパ組織 / バイエル板 / リンフォイドケモカイン / 原基 / 胚中心 / 経鼻ワクチン / 粘膜免疫 / 粘膜ワクチン / AIDSワクチン / 分泌型IgA / 経口ワクチン
Research Abstract

鼻咽腔関連リンパ組織(nasopharynx-associated lymphoid tissue ; NALT)は、腸管におけるパイエル板と同様の粘膜関連リンパ組織の一つである。上気道の免疫監視機構の解明にはNALTの形成メカニズムを明らかにする事が不可欠である。
リンフォイドケモカイン(CXCL13,CCL19,CCL21)は二次リンパ組織の初期形成に必須である。まずNALTの初期形成におけるリンフォイドケモカインの役割について検討した。CXCL13欠損マウス胎生期の腸管にはCD3^-CD4^+CD45^+細胞の集積を認めず、その結果、バイエル板は形成されなかった。ところがCXCL13欠損マウスのNALT原基にはCD3^-CD4^+CD45^+細胞の集積が確認された。CCL19及びCCL21の発現不全マウスであるpltマウスのNALT原基にはコントロールマウスと同等のCD3^-CD4^+CD45^+細胞の集積を認めた。以上の結果からリンフォイドケモカインはNALT初期形成に関与しないことが明らかとなった。
リンフォイドケモカインはリンパ組織構築の成熟化に重要な役割を果たしている。そこで我々はNALT組織構築への関与について検討した。CXCL13欠損マウスでは特にB細胞の遊走が傷害されており、NALTのB細胞領域がほとんど認められなかった。コレラトキシンを用いた経鼻免疫によりコントロールマウスのNALTには胚中心が形成されるが、CXCL13欠損マウスのNALTには胚中心は認められなかった。一方でpltマウスのNALTはT細胞領域の形成不全を認めた。以上の結果から胚中心形成やT/B細胞領域などNALT組織構築の成熟化にはリンフォイドケモカインが必須であることが明らかとなった。
このようにNALTの形成初期から成熟化にかけてリンフォイドケモカイン依存性の変化を示すことができた。

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (22 results)

All 2007 2006 2005

All Journal Article (22 results)

  • [Journal Article] Therapeutic effects of roxithromycin in interleukin-10-deficient colitis.2007

    • Author(s)
      Tamagawa, H. et al.
    • Journal Title

      Inflammatory Bowel Diseases 13・5

      Pages: 547-556

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intraepithelial lymphocytes : their shared and divergent immunological behaviors in the small and large intestine.2007

    • Author(s)
      Kunisawa, J. et al.
    • Journal Title

      Immunological Reviews 215

      Pages: 136-153

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intranasal immunization with phosphorylcholine induces antigen specific mucosal and systemic immune responses in mice.2007

    • Author(s)
      Tanaka, N. et al.
    • Journal Title

      Vaccine 25・14

      Pages: 2680-2687

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oral feeding of Bifidobacterium bifidum (BGN4) prevents CD4^+ CD45RB^<high> T cell-mediated inflammatory bowel disease by inhibition of disordered T cell activation.2007

    • Author(s)
      Kim, N.et al.
    • Journal Title

      Clinical Immunology 123・1

      Pages: 30-39

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production.2007

    • Author(s)
      Kunisawa, J, et al.
    • Journal Title

      Blood. 109・9

      Pages: 3749-3756

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gut lymphocyte migration : we are halfway 'home'.2007

    • Author(s)
      McGhee, J.R. et al.
    • Journal Title

      Trends in Immunology 28・4

      Pages: 150-153

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulatory role of Peyer's patches for the inhibition of OVA-induced allergic diarrhea.2007

    • Author(s)
      Takayama, N. et al.
    • Journal Title

      Clinical Immunology 123・2

      Pages: 199-208

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A second generation of double mutant cholera toxin adjuvants : enhanced immunity without intracellular trafficking.2006

    • Author(s)
      Hagiwara, Y. et al.
    • Journal Title

      Journal of Immunology 177・5

      Pages: 3045-3054

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cutting edge : Uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis.2006

    • Author(s)
      Fukuyama, S. et al.
    • Journal Title

      Journal of Immunology 177・7

      Pages: 4276-4280

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mucosal vaccine targeting improves onset of mucosal and systemic immunity to botulinum neurotoxin A.2006

    • Author(s)
      Maddaloni, M. et al.
    • Journal Title

      Journal of Immunology 177・8

      Pages: 5524-5532

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Innate immunity in the mucosal immune system.2006

    • Author(s)
      Nochi, T. et al.
    • Journal Title

      Current Pharmaceutical Design 12・32

      Pages: 4203-4213

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4+ T cells.2005

    • Author(s)
      Kai, Y., Takahashi, I., Ishikawa, H., Hiroi, T., Mizushima, T., Matsuda, C., Kishi, D., Hamada, H., Tamagawa, H., Ito, T., Yoshizaki, K., Kishimoto, T., Matsuda, H., Kiyono, H.
    • Journal Title

      Gastroenterology. 128

      Pages: 922-934

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prenatal blockage of lymphotoxin beta receptor and TNF receptor p55 signaling cascade resulted in the acceleration of tissue genesis for isolated lymphoid follicles in the large intestine.2005

    • Author(s)
      Kweon, M.N., Yamamoto, M., Rennert, P.D., Park, E.J., Lee, A.Y., Chang, S.Y., Hiroi, T., Nanno, M., Kiyono, H
    • Journal Title

      J.Immunol. 174

      Pages: 4365-4372

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intestinal gamma delta T cells develop in mice lacking thymus, all lymph nodes, Peyer's patches, and isolated lymphoid follicles.2005

    • Author(s)
      Nonaka, S., Naito, T., Chen, H., Yamamoto, M., Moro, K., Kiyono, H.
    • Journal Title

      J.Immunol. 174

      Pages: 1906-1912

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nasal IL-12p70 DNA prevents and treats intestinal allergic diarrhea.2005

    • Author(s)
      Hino, A., Fukuyama, S., Kataoka, K., Kweon, MN., Fujihashi, K.
    • Journal Title

      J.Immunol. 174

      Pages: 7423-7432

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Triggering of TLR3 by polyI:C in human corneal epithelial cells to induce inflammatory cytokines.2005

    • Author(s)
      Ueta, M., Hamuro, J., Kiyono, H., Kinoshita, S.
    • Journal Title

      Biochem.Biophys.Res.Commun. 331

      Pages: 285-294

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nontoxic Shiga toxin derivatives from Escherichia coli possess adjuvant activity for the augmentation of antigen-specific immune responses via dendritic cell activation.2005

    • Author(s)
      Ohmura, M., Yamamoto, M., Tomiyama -Miyaji, C., Yuki, Y., Takeda, Y., Kiyono, H.
    • Journal Title

      Infect.Immun. 73

      Pages: 4088-4097

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th-2 mediated IgE responses.2005

    • Author(s)
      Takagi, H., Hiroi, H., Yang, L., Tada, Y., Yuki, Y., Takamura, K., Ishimitsu, R., Kawauchi, H., Kiyono, H., Takaiwa, F.
    • Journal Title

      Proc.Nat.Acad.Sci.USA. 102

      Pages: 17525-17530

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Production of a recombinant cholera toxin B subunit-insulin B chain peptide hybrid protein by Brevibacillus choshinensis expression system as a nasal vaccine against autoimmune diabetes.2005

    • Author(s)
      Yuki, Y., Hara-Yakoyama, C., Guadiz, AA., Udak, S., Kiyono, H.
    • Journal Title

      Biotechnol.Bioeng. 92

      Pages: 803-809

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel neurotoxoid vaccine prevents mucosal botulism.2005

    • Author(s)
      Kobayashi, R., Kohda, T., Kataoka, K., Ihara, H., Kozaki, S., Pascual, DW., Staats, HF., Kiyono, H., McGhee, JR., Fujihashi K.
    • Journal Title

      J.Immunol. 174

      Pages: 2190-2195

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense.2005

    • Author(s)
      Kunisawa, J., Kiyono, H.
    • Journal Title

      Cell Mol.Life Sci 62

      Pages: 1308-1321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mucosa-associated lymphoid tissues in the aerodigestive tract : their shared and divergent traits and their importance to the orchestration of the mucosal immune system.2005

    • Author(s)
      Kunisaw, J., Fukuyama, S., Kiyono, H.
    • Journal Title

      Curr.Mol.Med. 5

      Pages: 557-572

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2018-03-28  

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