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Investigation and therapeutic application of ICOS and ICOSL in systemic sclerosis

Research Project

Project/Area Number 21591456
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKanazawa University

Principal Investigator

HASEGAWA Minoru  金沢大学, 附属病院, 講師 (50283130)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords強皮症 / 線維化 / ICOS / ICOSL / ブレオマイシン / 皮膚 / 肺 / サイトカイン / ICOS ligand / マウス
Research Abstract

We assessed the roles of ICOS and ICOSL in tissue fibrosis by administering bleomycin intratracheally or intradermally into ICOS and/or ICOSL-deficient mice. The loss of ICOS attenuated fibrosis of lungs and skin, whereas deficiency of ICOSL aggravated it. Mice deficient in both ICOS and ICOSL also exhibited accelerated fibrosis, reflecting a dominant role for ICOSL over ICOS in this model. ICOSL expression on macrophages and B cells in bronchoalveolar fluids was significantly elevated in ICOS-deficient mice compared to wild type mice during this process. Thus, ICOSL expression levels on B cells and macrophages were inversely associated with the severity of tissue fibrosis. Our results indicate that ICOSL expression on antigen presenting cells plays a previously unknown regulatory role during the development of bleomycin-induced tissue fibrosis which is independent of the ICOS-ICOSL pathway.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (9 results)

All 2011 2010 2009

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (3 results)

  • [Journal Article] Serum chemokine and cytokine levels as indicators of disease activity in patients with systemic sclerosis.2011

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

      Clin Rheumatol

      Volume: 30 Pages: 231-237

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dermoscopy findings of nail fold capillaries in connective tissue diseases2011

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

      J Dermatol

      Volume: 38 Pages: 66-70

    • NAID

      10027902799

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inducible costimulator ligand(ICOSL) regulates bleomycin-induced Lung and skin fibrosis independently of the ICOS-ICOSL pathway2010

    • Author(s)
      Tanaka C, Fujimoto M, Hamaguchi Y, Sato S, Takehara K, Hasegawa M
    • Journal Title

      Arthritis Rheum

      Volume: 62 Issue: 6 Pages: 1723-32

    • DOI

      10.1002/art.27428

    • NAID

      10029469768

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] B lymphocytes : shedding new light on the pathogenesis of systemic sclerosis2010

    • Author(s)
      Hasegawa M.
    • Journal Title

      J Dermatol 37

      Pages: 3-10

    • NAID

      10027064811

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosis2009

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

      Arthritis Rheum 60

      Pages: 3465-75

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced red blood cell velocity in nail-fold capillaries as a sensitive and specific indicator of microcirculation injury in systemic sclerosis2009

    • Author(s)
      Mugii N, Hasegawa M, et al.
    • Journal Title

      Rheumatology (Oxford) 48

      Pages: 696-703

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Augmented ICOS-ICOS ligand signaling axis in patients with early diffuse cutaneous systemic sclerosis2011

    • Author(s)
      Hasegawa M, Matsushita T, Hamaguchi Y, Fujimoto M, Takehara K
    • Organizer
      ACR/ARHP Scientific Meeting
    • Place of Presentation
      マコーミックプレイス(シカゴ、USA)
    • Year and Date
      2011-11-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Augmented ICOS-ICOS ligand signaling axis in patients with early diffuse cutaneous systemic sclerosis2011

    • Author(s)
      Minoru Hasegawa
    • Organizer
      ACR/AEHP Scientific Meeting
    • Place of Presentation
      マコーミックプレイス(シカゴ、USA)
    • Year and Date
      2011-11-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel inhibitor of TGF-β/Smad signaling attenuates tissue fibrosis in mouse models of systemic sclerosis2010

    • Author(s)
      Hasegawa M, et al.
    • Organizer
      1'st Systemic Sclerosis World Congress
    • Place of Presentation
      フィレンツェ (イタリア)
    • Year and Date
      2010-02-12
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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