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Elucidation of the molecular mechanisms of CD4 T cell-induced osteoblastic hematopoietic niche impairments after bone marrow transplantation

Research Project

Project/Area Number 23790432
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

UEHA Satoshi  東京大学, 大学院・医学系研究科, 助教 (00447385)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords炎症 / 移植免疫 / 造血幹細胞 / GVHD / 骨芽細胞
Research Abstract

Using mouse allo-HSCT models, we revealed that fibroblasts/mesenchymal stem cells as well as osteoblasts were damaged early after allo-HSCT, and that the recovery of osteoblasts from X-ray irradiation-mediated damage was impaired in mice with GVHD. The osteoblast impairments were partially dependent on MHC class II on host non-hematopoietic cells, whereas the killing and growth inhibition of osteoblast cell lines required activation of allo-CD4 T cells. Based on gene expression analyses, we identified an osteoblast inhibitory factor, which was specifically expressed in allo-CD4 T cells, as a candidate mediator of osteoblast impairment during BM GVHD. We expect that our results would contribute to the development of early diagnostic markers as well as the preventive and therapeutic strategies against BM GVHD.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (14 results)

All 2012 2011

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Invited: 1 results)

  • [Journal Article] Roles of chemokine receptor CX3CR1 in maintaining murine bone homeostasis through the regulation of both osteoblasts and osteoclasts2012

    • Author(s)
      Hoshino A. Ueha S. Hanada S. Imai T. Ito M. Yamamoto K. Matsushima K. Yamaguchi A. Iimura T
    • Journal Title

      J Cell Sci

      Volume: 15;126(Pt 4) Pages: 1032-45

    • DOI

      10.1242/jcs.113910

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin.2012

    • Author(s)
      Keisuke Nagao
    • Journal Title

      Nature Immunology

      Volume: 13(8) Issue: 8 Pages: 744-752

    • DOI

      10.1038/ni.2353

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis2012

    • Author(s)
      Ueha S
    • Journal Title

      Front Immunol

      Volume: 3 Pages: 71-71

    • DOI

      10.3389/fimmu.2012.00071

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 骨髄GVHD2012

    • Author(s)
      上羽悟史
    • Journal Title

      医学のあゆみ

      Volume: 242 Pages: 671-676

    • Related Report
      2012 Final Research Report
  • [Presentation] Bone marrow dysfunction and defective B lymphopoiesis during chronic GVHD2012

    • Author(s)
      小杉瑞葉
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸国際展示場(兵庫)
    • Year and Date
      2012-12-05
    • Related Report
      2012 Final Research Report
  • [Presentation] Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation2012

    • Author(s)
      小杉瑞葉
    • Organizer
      第34回日本炎症再生医学会
    • Place of Presentation
      ホテル日航福岡(福岡)
    • Year and Date
      2012-07-05
    • Related Report
      2012 Final Research Report
  • [Presentation] Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation2012

    • Author(s)
      Mizuha Kosugi
    • Organizer
      The 33th Annual Meeting on the Japanese Society of Inflammation and Regeneration
    • Place of Presentation
      福岡県(ホテル日航福岡 )
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Bone marrow dysfunction and defective B lymphopoiesis during chronic GVHD2012

    • Author(s)
      Mizuha Kosugi
    • Organizer
      The 41st Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      兵庫県(神戸国際展示場)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Lymph node graft-versushost disease: CD8+ T cell-mediated destruction of lymph nodes after allogeneic hematopoietic stem cell transplantation2011

    • Author(s)
      末永文子
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕 張メッセ、千葉
    • Year and Date
      2011-11-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Pre-conditioning and the Immune Response Cooperatively Impair the Osteoblastic Hematopoietic Niche in Murine Bone Marrow Graft-versus-host Disease2011

    • Author(s)
      WANG Yong
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ、千葉
    • Year and Date
      2011-11-27
    • Related Report
      2012 Final Research Report
  • [Presentation] Bone marrow graft-versus-host disease: immune attack to osteoblastic hematopoietic niche after allogeneic hematopoietic stem cell transplantation2011

    • Author(s)
      上羽悟史
    • Organizer
      19th International Symposium on Molecular Cell Biology of Macrophages.
    • Place of Presentation
      全日空ゲートタワーホテル大阪、大阪
    • Year and Date
      2011-05-25
    • Related Report
      2012 Final Research Report
  • [Presentation] Bone marrow graft-versus-host disease: immune attack to osteoblastic hematopoietic niche after allogeneic hematopoietic stem cell tansplantation2011

    • Author(s)
      UEHA Satoshi
    • Organizer
      19th International Symposium on Molecular Cell Biology of Macrophages(招待講演)
    • Place of Presentation
      全日空ゲートタワーホテル大阪、大阪府
    • Related Report
      2011 Research-status Report
  • [Presentation] Pre-conditioning and the Immune Response Cooperatively Impair the Osteoblastic Hematopoietic Niche in Murine Bone Marrow Graft-versus-host Disease2011

    • Author(s)
      WANG Yong
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ、千葉県
    • Related Report
      2011 Research-status Report
  • [Presentation] Lymph node graft-versus host disease: CD8+ T cell-mediated destruction of lymph nodes after allogeneic hematopoietic stem cell transplantation2011

    • Author(s)
      SUENAGA Fumiko
    • Organizer
      第40回日本免疫学会学術総会
    • Place of Presentation
      幕張メッセ、千葉県
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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