• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

内因性制御リガンドと受容体の探索およびマスト細胞依存的炎症性疾患への応用

Research Project

Project/Area Number 11J04859
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

倉島 洋介  東京大学, 医科学研究所, 助教

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2013: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2012: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2011: ¥800,000 (Direct Cost: ¥800,000)
Keywordsマスト細胞 / 内因性制御リガンド / 皮膚炎 / ビタミンA / 線維芽細胞 / P2X7受容体 / 炎症性疾患 / ホッキョクグマ / 細胞外核酸 / 皮膚
Research Abstract

本研究課題では、P2X7受容体の発現機構の解明を目的とし、皮膚に存在する内因性制御リガンド・センサー(受容体)の同定と、マスト細胞におけるP2X7受容体の発現・機能制御分子について解析を行った。
まず、研究初年度~次年度においては、マスト細胞上のP2X7受容体の発現を抑制する機能が初代培養皮膚線維芽細胞に存在していることを見出した。さらに、腸管間質細胞など他の組織に存在する間質細胞と比較するために遺伝子プロファイリングを行った結果、皮膚線維芽細胞がレチノイド分解酵素を有意に高く発現していることが明らかとなった。つまり、皮膚線維芽細胞のレチノイド分解酵素がP2X7受容体の発現および機能制御に深く関与していることを見出した。最終年度においては、レチノイド分解酵素によるP2X7受容体の発現抑制機序の破綻が、マウスにおいて皮膚炎を導くことが明らかにした。これは、高濃度のビタミンA摂取によるレチノイド過剰症ならびにレチノイン酸療法の副作用である皮膚炎症のメカニズムの一つとして考えられ、炎症疾患の発症機構のみならず、レチノイン酸療法の合併症に対する予防法の可能性として示される。
本研究により成果は、マスト細胞の組織特有の機能制御機構を初めて明らかとしたもので、今後、組織特異的な疾患の発症機序の解明および慢性炎症性疾患の新たな治療法確立につながると期待される。
研究成果の一部については、国内および国際学会で発表をしており、主な内容はImmunity誌・201440 (4) : 530-541に発表している。

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

3年弱の研究期間で論文発表に至るまで研究を遂行できた。本成果はマスト細胞の組織特有の機能制御機構を新たに見出したものであり、組織特異的な疾患の発症機序の解明および治療法確立の基盤となる可能性を秘めた点においては、達成度が高いものであると考えられる。

Strategy for Future Research Activity

間質細胞との相互作用による免疫細胞の組織特異性の獲得機序の更なる解析から得られる成果が、慢性炎症に対する効果的な治療法の開発につながることを期待している。

Report

(3 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (24 results)

All 2014 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (13 results) (of which Invited: 1 results) Book (2 results) Remarks (3 results)

  • [Journal Article] The enzyme cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis.2014

    • Author(s)
      Kurashima Y, Amiya T, Fjisawa K, Shibata N, Suzuki Y, Kogure Y, Hashimoto E, Otsuka A, Kabashima K, Sato S, Sato T, Kubo M, Akira S, Miyake K, Kunisawa J, Kiyono H.
    • Journal Title

      Immunity

      Volume: 40 Issue: 4 Pages: 530-541

    • DOI

      10.1016/j.immuni.2014.01.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] New era for mucosal mast cells : their roles in inflammation, allergic immune rasposes and adjuvant development.2014

    • Author(s)
      Kurashima Y, Kiyono H.
    • Journal Title

      Exp Mol Med.

      Volume: 46 Issue: 3 Pages: e83-e83

    • DOI

      10.1038/emm.2014.7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation.2013

    • Author(s)
      Kurashima Y, Goto Y, Kiyono H.
    • Journal Title

      Eur J Immunol.

      Volume: 12 Issue: 12 Pages: 3108-3115

    • DOI

      10.1002/eji.201343782

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice2013

    • Author(s)
      J. Kunisawa, M. Gohda, E. Hashimoto, I. Ishikawa, M. Higuchi, Y. Suzuki, Y. Goto, C. Panea, I. I. Ivanov, R. Sumiya, L. Aayam, T. Wake, S. Tajiri, Y. Kurashima, S. Shikata、S. Akira, K. Takeda, H. Kiyono
    • Journal Title

      Nat Commun.

      Volume: 10-1038 Issue: 1 Pages: 1038-1038

    • DOI

      10.1038/ncomms2718

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors2012

    • Author(s)
      Y. Kurashima, T. Amiya, T. Nochi, K. Fujisawa, T. Haraguchi, H. Iba, H. Tsutsui, S. Sato, S. Nakajima, H. Iijima, M. Kubo, J. Kunisawa, H. Kiyono
    • Journal Title

      Nat Commun.

      Volume: 3-1034 Issue: 1 Pages: 1034-1034

    • DOI

      10.1038/ncomms2023

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gut-associated lymphoid tissues for the development of oral vaccines2012

    • Author(s)
      Jun Kunisawa, Yosuke Kurashima, Hiroshi Kiyono
    • Journal Title

      Adv Drug Deliv Rev

      Volume: 64 Pages: 523-530

    • Related Report
      2011 Annual Research Report
  • [Presentation] マスト細胞の組織特異性の獲得と機能制御2014

    • Author(s)
      倉島洋介
    • Organizer
      第23回東京フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2014-02-24
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Retinoic acid metabolism regulates ATP/P2X7-mediated mast cell activation for the maintenance of skin homeostasis2013

    • Author(s)
      Kurashima Y, Amiya T, Kogure Y, Sato S, Kunisawa J, and Kiyono H.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2013-12-13
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molucular and cellular analysis of symbiotic co-habitation with environmental bacteria in the colonic resident macrophage2013

    • Author(s)
      Takahashi I, Yamamoto D, Kurashima Y, Shibata N, Nagatake T, Sato S, Kunisawa J, Maruyama F, Nakagawa I, Abe A, and Kiyono H
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2013-12-13
    • Related Report
      2013 Annual Research Report
  • [Presentation] S1P1 is required for B cell- receptor- and Toll- like receptor - mediated B cell activations2013

    • Author(s)
      Akashi-Takemura S, Yamakawa N, Tanimura N, Shibata T, Amiya T, Kurashima Y, Kunisawa J, Kiyono H, Suzuki K, Kikuta J, Ishii M, Proia LR, Takuwa Y, and Miyake K
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2013-12-12
    • Related Report
      2013 Annual Research Report
  • [Presentation] PILRa negatively regulates DSS induced experimental colitis2013

    • Author(s)
      Kishida K, Kohyama M, Kurashima Y, Wang J, Hirayasu K, Suenaga T, Kiyono H, Kunisawa J, and Arase H
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2013-12-11
    • Related Report
      2013 Annual Research Report
  • [Presentation] Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors in mice2012

    • Author(s)
      Y. Kurashima
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      兵庫,日本(招待講演)
    • Year and Date
      2012-12-03
    • Related Report
      2012 Annual Research Report
  • [Presentation] Acceleration of Intestinal Inflammatory Responses by Extracellular Nucleotides-mediated Mast Cell Activation2012

    • Author(s)
      Y. Kurashima, T. Amiya, J. Kunisawa and H. Kiyono
    • Organizer
      19th East Asia Joint Symposium on Biomedical Research ″Molecular Understandings for Physiology
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2012-08-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors in mice2012

    • Author(s)
      Y. Kurashima, T. Amiya, K. Fujisawa, J. Kunisawa, and H
    • Organizer
      Purine 2012, International Symposium on Purinergic Signaling in New Strategy of Drug Discovery
    • Place of Presentation
      福岡,日本
    • Year and Date
      2012-06-05
    • Related Report
      2012 Annual Research Report
  • [Presentation] Indigenous environmental bacteria involve the creation of mucosal homeoatasis2011

    • Author(s)
      H.Toubou, I.Takahashi, Y.Goto, Y.Kurashima, H.
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉,幕張
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Dietary vitamin B1 is required for the maintenance of naive B cells but not intestinal IgA-secreting plasma cells2011

    • Author(s)
      I.Wake, I.Kurashima, J.Kunisawa, H.Kiyono
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉,幕張
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] AIP/P2X7 receptor-targeted activation of mast cells for control the intestinal inflammation2011

    • Author(s)
      I.Amiya, Y.Kurashima, J.Kunisawa, H.Kiyono
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉,幕張
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Extracellular AIP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors in mice2011

    • Author(s)
      Yosuke Kurashima, Takeaki Amiya, Jun Kunisawa, Hiroshi Kiyono
    • Organizer
      International Congress of Mucosal Immunology 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-07-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Unique pathways of purinergic P2X7 receptor-mediated colonic mast cell activation in the intestinal inflammation2011

    • Author(s)
      Yosuke Kurashima, Takeaki Amiya, Jun Kunisawa, Hiroshi Kiyono
    • Organizer
      Immunology 2011
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2011-05-01
    • Related Report
      2011 Annual Research Report
  • [Book] 臨床免疫・アレルギー科2013

    • Author(s)
      倉島洋介、國澤 純、清野 宏
    • Total Pages
      10
    • Publisher
      科学評論社
    • Related Report
      2013 Annual Research Report
  • [Book] 粘膜マスト細胞と疾患2012

    • Author(s)
      倉島洋介、國澤 純、清野 宏
    • Publisher
      最新医学社
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/imsut/jp/research/papers/cyp26bl.php

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.u-tokyo.ac.jp/public/public01_260411_j.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.jst.go.jp/pr/announce/20140411/

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2011-12-12   Modified: 2024-03-26  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi