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2015 Fiscal Year Annual Research Report

キチンの新規受容体の同定とシグナル伝達機構の解明

Research Project

Project/Area Number 15K15377
Research InstitutionNational Center for Child Health and Development

Principal Investigator

斎藤 博久  国立研究開発法人国立成育医療研究センター, 研究所, 副所長 (40130166)

Project Period (FY) 2015-04-01 – 2016-03-31
Keywordsキチン / Th2 / アレルギー
Outline of Annual Research Achievements

ダニはアレルギーの主要な抗原であるが、アレルギー性疾患の発症に関わるダニの成分には不明な点が多い。申請者は、マウスにおいて、タンパク質抗原単独ではアレルギーは誘導されないが、ダニの外殻構成成分「キチン」の存在下では、IL-33の発現誘導を介して、IL-4/13-STAT6経路依存的なアレルギー応答が惹起されことを見いだした。しかしながら、TLR2やDectin-1といった既知のキチン受容体が、本誘導機構に関与しない結果が得られている。そこで、本研究では、キチンによるアレルギー応答誘導に関わる新規キチン受容体の同定を目的とする。
キチンビーズを用いたアフィニティクロマトグラフィにより、マウスの肺タンパク質抽出液より、複数の特異的なキチン結合タンパク質(CBP)を得た。これらをLC-MS解析により同定した結果、一つはChitinase-like protein 1(Chil1, CHI3L1, BRP-39)であった。そこで、このChil1がキチン依存的な自然免疫細胞の活性化に関与するかをin vitroで検討した。マウスに生理食塩水、キチン、Chil1もしくはChil1+キチンを経鼻的に1回だけ投与すると、Chil1+キチン投与マウスでのみ、気道への強い顆粒球浸潤が誘導された。さらにin vitroにおいて、マウス骨髄由来樹状細胞(BMDC)をメディウム、キチン、Chil1もしくはChil1+キチンで刺激すると、Chil1+キチン刺激でのみ、BMDCによる炎症性サイトカイン産生が誘導された。これらの結果から、Chil1がセンサー分子としてキチンのシグナル伝達機構に関与し、キチンによる自然免疫応答の活性化とそれに続くアレルギー応答誘導に関与すると考えられた。今後は、このChil1が実際にOVA・キチンによるアレルギー誘導に関与するかを検討するため、Chil1欠損マウスの作製に着手する。さらに、キチン-Chil1複合体が結合する何らかの新規受容体が存在し、キチンによるアレルギー誘導に関与すると考えられた。

  • Research Products

    (13 results)

All 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results)

  • [Int'l Joint Research] SIAF(Switzerland)

    • Country Name
      Switzerland
    • Counterpart Institution
      SIAF
  • [Int'l Joint Research] Stanford University School of Medicine/Departments of Pathology(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Stanford University School of Medicine/Departments of Pathology
  • [Int'l Joint Research] Cambridge/MRC Laboratory of Molecular Biology(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      Cambridge/MRC Laboratory of Molecular Biology
  • [Journal Article] Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation.2016

    • Author(s)
      Takeda T, Unno H, Morita H, Futamura K, Emi-Sugie M, Arae K, Shoda T, Okada N, Igarashi A, Inoue E, Kitazawa H, Nakae S, Saito H, Matsumoto K, Matsuda A.
    • Journal Title

      J Allergy Clin Immunol

      Volume: in Press Pages: in Press

    • DOI

      10.1016/j.jaci.2016.01.032

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sera of patients with infantile eosinophilic gastroenteritis showed a specific increase in both thymic stromal lymphopoietin and IL-33 levels.2016

    • Author(s)
      Shoda T, Matsuda A, Arai K, Shimizu H, Morita H, Orihara K, Okada N, Narita M, Ohya Y, Saito H, Matsumoto K, Nomura I.
    • Journal Title

      J Allergy Clin Immunol

      Volume: in Press Pages: in Press

    • DOI

      10.1016/j.jaci.2015.11.042

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation.2016

    • Author(s)
      Shoda T, Futamura K, Orihara K, Emi-Sugie M, Saito H, Matsumoto K, Matsuda A.
    • Journal Title

      Allergol Int

      Volume: 65 Pages: 21-9

    • DOI

      10.1016/j.alit.2015.08.001

    • Peer Reviewed / Open Access
  • [Journal Article] Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations.2016

    • Author(s)
      Horimukai K, Morita K, Narita M, Kondo M, Kabashima S, Inoue E, Sasaki T, Niizeki H, Saito H, Matsumoto K, Ohya Y.
    • Journal Title

      Allergol Int

      Volume: 65 Pages: 103-8

    • DOI

      10.1016/j.alit.2015.09.004

    • Peer Reviewed / Open Access
  • [Journal Article] IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice.2015

    • Author(s)
      Morita H, Arae K, Unno H, Toyama S, Motomura K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Saito H, Matsumoto K, Nakae S.
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0134226

    • DOI

      10.1371/journal.pone.0134226

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers.2015

    • Author(s)
      Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie AN, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S.
    • Journal Title

      Immunity

      Volume: 43 Pages: 175-86

    • DOI

      10.1016/j.immuni.2015.06.021

    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Measurement of allergen-specific secretory IgA in stool of neonates, infants and toddlers by protection against degradation of immunoglobulins and allergens.2015

    • Author(s)
      Kamemura N, Takashima M, Morita H, Matsumoto K, Saito H, Kido H.
    • Journal Title

      J Med Invest

      Volume: 62 Pages: 137-44

    • DOI

      10.2152/jmi.62.137

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies.2015

    • Author(s)
      Horimukai K, Hayashi K, Tsumura Y, Nomura I, Narita M, Ohya Y, Saito H, Matsumoto K.
    • Journal Title

      Allergy

      Volume: 70 Pages: 334-7

    • DOI

      10.1111/all.12562

    • Peer Reviewed
  • [Journal Article] Global DNA hypomethylation coupled to cellular transformation and metastatic ability.2015

    • Author(s)
      Funaki S, Nakamura T, Nakatani T, Umehara H, Nakashima H, Okumura M, Oboki K, Matsumoto K, Saito H, Nakano T.
    • Journal Title

      FEBS Lett

      Volume: 589 Pages: 4053-60

    • DOI

      10.1016/j.febslet.2015.11.020

    • Peer Reviewed
  • [Journal Article] Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation.2015

    • Author(s)
      Ebihara T, Azuma M, Oshiumi H, Kasamatsu J, Iwabuchi K, Matsumoto K, Saito H, Taniguchi T, Matsumoto M, Seya T.
    • Journal Title

      J Exp Med

      Volume: 212 Pages: 1337

    • DOI

      10.1084/jem.2009157307012015c

    • Peer Reviewed

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Published: 2017-01-06   Modified: 2022-01-31  

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