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Decoy receptor for IL-21 ameliorates GVHD

Research Project

Project/Area Number 19591131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJichi Medical University

Principal Investigator

OZAKI Katsutoshi  Jichi Medical University, 医学部, 講師 (10286453)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords血液免疫学 / 免疫制御 / IL-21 / GVHD / GVL
Research Abstract

これまでの研究成果(平成17-18 年若手研究B)からIL-21R を欠損した脾細胞を用いると誘導されるGVHD が減弱することが示されている。つまりIL-21 シグナルのない状態ではGVHD は引き起こされにくいと考えられたため、GVHD を予防、治療するためにIL-21 のデコイ受容体を作成し、骨髄細胞に強制発現させ移植を行った。デコイ受容体は細胞内ドメインの大部分を欠損させたため、リガンドであるIL-21 と結合はするものの、シグナルを伝達しない。生理的なIL-21 と結合し、その機能を競合的に抑制することが期待された。実際、in vitroの実験ではデコイ受容体は上清中のIL-21 の濃度低下をもたらした。マウスを用いた移植実験では、コントロールベクターを感染させた場合と比較するとデコイ受容体は有意に生存率を上昇させることが明らかとなった。デコイ受容体はIL-21 のシグナルを抑制することで、GVHDを抑制し、生存率を高めたと推察された。このことはIL-21 のシグナルの阻害がGVHD の予防、治療に応用できる可能性を示している。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (13 results)

All 2009 2008 2007

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (5 results)

  • [Journal Article] Prediction of response t o imatinib in patients with chronic mye logenous leukemia by flow cytometric an alysis of bone marrow blastic cell phen otypes2009

    • Author(s)
      Oka S, Muroi K, Mori M, Matsuyama T, Fujiwara S, Oh I, Sato K, Kikuchi S, Ue da M, Toshima M, Suzuki T, Ozaki K, Nagai T, Ozawa K
    • Journal Title

      Leuk Lymphoma. 50(2)

      Pages: 290-29

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma2009

    • Author(s)
      Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, Nobuyoshi M, Oh I, Sato K, Suzuki T, Ozaki K, Mori M, Nagai T, Muroi K, Kano Y, Furukawa Y, Ozawa K
    • Journal Title

      Oncogene 28(2)

      Pages: 231-242

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of response to imatinib in patients with chronic myelogenous leukemia by flow cytometric analysis of bone marrow blastic cell phenotypes.2009

    • Author(s)
      Oka S, Muroi K, Mori M, Matsuyama T, Fujiwara S, Oh I, Sato K, Kikuchi S, Ueda M, Toshima M, Suzuki T, Ozaki K, Nagai T, Ozawa K
    • Journal Title

      Leuk Lymphoma 50(2)

      Pages: 290-293

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma.2008

    • Author(s)
      Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, Nobuyoshi M, Oh I, Sato K, Suzuki T, Ozaki K, Mori M, Nagai T, Muroi K, Kano Y, Furukawa Y, Ozawa K
    • Journal Title

      Oncogene. 28(2)

      Pages: 231-242

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell and gene therapy using mesenchymal stem cells (MSCs).2008

    • Author(s)
      Ozawa K, Sato K, Oh I, Ozaki K, Uchibori R, Obara Y, Kikuchi Y, Ito T, Okada T, Urabe M, Mizukami H, Kume A
    • Journal Title

      J Autoimmun. 30(3)

      Pages: 121-127

    • Related Report
      2008 Annual Research Report 2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Screening of genes responsible for differentiation of mouse mesenchymal stromal cells by DNA micro-array analysis of C3H10T1/2 and C3H10T1/2-derived cell lines.2007

    • Author(s)
      Oh I, Ozaki K, Miyazato A, Sato K, Meguro A, Muroi K, Nagai T, Mano H, Ozawa K
    • Journal Title

      Cytotherapy 9

      Pages: 80-90

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide plays a critical role in suppression of T cell proliferation by mesenchy mal stem cells.2007

    • Author(s)
      Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, Muroi K, Ozawa K
    • Journal Title

      Blood 109

      Pages: 228-234

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells.2007

    • Author(s)
      Oh I, Ozaki K, Sato K, Meguro A, Tatara R, Hatanaka K, Nagai T, Muroi K, Ozawa K
    • Journal Title

      Biochem Biophys Res Commun 355

      Pages: 956-962

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Blocking of IL-21 signal attenuates graft-versus-host disease but not graft-versus-leukemia effect in a mouse model.2008

    • Author(s)
      Meguro A, Ozaki K, Oh I, Matsu H, Hatanaka K, Tatara R, Leonard WJ, Sato K, Ozawa K
    • Organizer
      2008 Annual Meeting of ASH(Blood 2008;112(11): 453a)
    • Place of Presentation
      San Francisco, CA,
    • Year and Date
      2008-12-07
    • Related Report
      2008 Final Research Report
  • [Presentation] Blocking of IL-21 signal attenuates graft-versus-host disease but not graft-versus-leukemia effect in a mouse model.2008

    • Author(s)
      Meguro A, Ozaki K, Oh I, Matsu H, Hatanaka K, Tatara R, Leonard WJ, Sato K, Ozawa K
    • Organizer
      2008 Annual Meeting of ASH at San Francisco, CA
    • Place of Presentation
      Moscone Center
    • Year and Date
      2008-12-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Blocking of IL-21 signal attenuates graft-versus-host disease but not graft-versus-leukemia effect in a mouse model.2008

    • Author(s)
      Meguro A, Ozaki K, Oh I, Matsu H, Hatanaka K, Sato K, Tatara R, Suzuki T, Mori M, Nagai T, Muroi K, Ozawa K
    • Organizer
      第67 回日本癌学会学術総会(O-181, Program p87)
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2008 Final Research Report
  • [Presentation] Blocking of IL-21 signal attenuates graft-versus-host disease but not graft-versus-leukemia effect in a mouse model.2008

    • Author(s)
      Meguro A, Ozaki K, Oh I, Matsu H, Hatanaka K, Sato K, Tatara R, Suzuki T, Mori M, Nagai T, Muroi K, Ozawa K
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] GVHDにおけるIL-21の役割2007

    • Author(s)
      目黒 明子, 尾崎 勝俊, 翁 家国, 佐藤 一也, 多々良 礼音, 松 春子, 畑中 恵子, 鈴木 隆浩, 森 政樹, 永井 正, 室井 一男, 小澤 敬也
    • Organizer
      日本血液学会日本臨床血液学会合同総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-11
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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