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Development of a novel therapeutic strategy for allergic disorders by targeting human hematopoietic progenitors

Research Project

Project/Area Number 18604006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field アレルギー
Research InstitutionKyushu University

Principal Investigator

IWASAKI Hiromi  Kyushu University, Hospital, Assistant Professor (20403925)

Co-Investigator(Kenkyū-buntansha) AKASHI Koichi  Kyushu University, Graduate School of Medical Sciences, Professor (80380385)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordseosinophil / basophil / mast cell / Progenitor / transcription factor / allergy / hypereosinophilic syndrome / Hypereosinophilic syndrome
Research Abstract

To establish effective therapeutic strategies for eosinophil-related disorders including allergic reactions and hypereosinophilic syndrome (HES) ,it should be important to understand the developmental pathway of human eosinophils by defining their lineage-committed progenitors. Here we isolate the human eosinophil lineage-committed progenitors (hEoPs) in the steady-state bone marrow according to the expression of Interleukin-5 receptor alpha chain (IL-5Rα) .IL-5Rα^+CD34^+CD38^+ hEoPs constituted 〜10% of the human common myeloid progenitor (hCMP) population, and gave rise exclusively to pure eosinophil colonies at 〜20% plating efficiency. Although blood basophils expressed IL-5Rα at a high level, progeny of IL-5Rα^+CD34^+CD38^+ cells never included histidine decarboxylase-expressing basophils. hEoPs developed in the culture of IL-5Rα- hCMPs, while neither megakaryocyte/erythrocyte progenitors nor granulocyte/macrophage progenitors, both of which develop downstream of hCMPs, generated CC … More chemokine receptor 3-expressing eosinophils in vitro. These observations indicate that the human eosinophil lineage diverges at the hCMP stage as a distinct pathway from the megakaryocyte/erythrocyte and the neutrophil/macrophage lineages. At this branchpoint, hEoPs upregulated GATA-1 and GATA-2 but not Friend of GATA-1. To clarify the physiological contribution of hEoPs to eosinophilopoiesis, we analyzed bone marrow samples from eosinophilia patients. The proportion of hEoPs in CD34^+ bone marrow progenitors 3-fold increased in eosinophilia patients including HES as compared with that in normal bone marrows (7.44 % vs. 2.38 %, p<0.01) .These data suggest that the hEoP stage is necessary for eosinophil differentiation and expansion, and that hEoPs might be a powerful tool to study pathogenesis of eosinophilia, and even be a critical therapeutic target in eosinophil-related disorders. To find the molecules that play critical roles in the hEoP development, we are planning to analyze the gene expression profile of hEoPs by the DNA microarray methodology. We are also trying to identify the human basophil/mast cell progenitor. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006 Other

All Journal Article (14 results) (of which Peer Reviewed: 5 results) Presentation (5 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage2008

    • Author(s)
      Cantor AB, et. al.
    • Journal Title

      The Journal of Experimental Medicine 205(3)

      Pages: 611-624

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Antagonism of FOG-1 and GATA factors in fate choice for the mast cell Lineage2008

    • Author(s)
      Cantor AB, et. al.
    • Journal Title

      The Journal of Experimental Medicine 205(3)

      Pages: 611-624

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Myeloid lineage commitment from the hematopoietic stem cell2007

    • Author(s)
      Iwasaki H, et. al.
    • Journal Title

      Immunity 26(6)

      Pages: 726-740

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hematopoietic developmental pathways: on cellular basis2007

    • Author(s)
      Iwasaki H, et. al.
    • Journal Title

      Oncogene 26(47)

      Pages: 6687-6696

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 転写因子による造血制御2007

    • Author(s)
      岩崎 浩己
    • Journal Title

      血液・腫瘍科 54(6)

      Pages: 641-646

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Journal Article] 好酸球の分化機構2007

    • Author(s)
      森 康雄, 他
    • Journal Title

      Biotherapy 21(3)

      Pages: 181-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The developmental pathways of eosinophil, basophil, and mast cell lineages2007

    • Author(s)
      Iwasaki, H, et. al.
    • Journal Title

      Annual Review Hematology 2007

      Pages: 121-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hematopoietic developmental pathways : on cellular basis2007

    • Author(s)
      Iwasaki H, et. al.
    • Journal Title

      Oncogene 26(47)

      Pages: 6687-6696

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The lineage-instructive transcription factors in hematopoiesis.2007

    • Author(s)
      Iwasak H
    • Journal Title

      Hematology & Oncology 54(6)

      Pages: 641-646

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The developmental pathway of eosinophil lineage2007

    • Author(s)
      Mori Y, et. al.
    • Journal Title

      Biotherapy 21(3)

      Pages: 181-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hematopoietic developmental pathways on cellular basis2007

    • Author(s)
      Iwasaki H, et. al.
    • Journal Title

      Oncogene 26(47)

      Pages: 6687-6696

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 好酸球の分化機構2007

    • Author(s)
      森 康雄, et. al.
    • Journal Title

      Biotherapy 21(3)

      Pages: 181-186

    • Related Report
      2007 Annual Research Report
  • [Journal Article] The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages2006

    • Author(s)
      Iwasaki H, et. al.
    • Journal Title

      Genes & Development 20(21)

      Pages: 3010-3021

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The order of expression of transcription factors directs hierarchica specification of hematopoictic lineages.2006

    • Author(s)
      Iwasaki H, et al.
    • Journal Title

      Genes & Development 20(21)

      Pages: 3010-21

    • Related Report
      2006 Annual Research Report
  • [Presentation] ヒト好酸球前駆細胞の同定2007

    • Author(s)
      森 康雄
    • Organizer
      第69回 日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of the human eosinophil lineage-committed progenitor2007

    • Author(s)
      Mori Y.
    • Organizer
      The Japanese Society of Hematology 69th Annual Meeting
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト好酸球前駆細胞の同定2007

    • Author(s)
      森 康雄
    • Organizer
      第69回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Prospective isolation of human eosinophil-committed progenitors2006

    • Author(s)
      Mori Y.
    • Organizer
      第48回 米国血液学会
    • Place of Presentation
      オーランド,米国
    • Year and Date
      2006-12-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Prospective isolation of human eosinophil-committed progenitors2006

    • Author(s)
      Mori Y
    • Organizer
      The American Society of Hematology 48th Annual Meeting
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2006-12-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review 血液 20072007

    • Author(s)
      岩崎 浩己, 他
    • Total Pages
      292
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review 血液2007

    • Author(s)
      岩崎 浩己, 他
    • Total Pages
      292
    • Publisher
      中外医学社
    • Related Report
      2006 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.med.kyushu-u.ac.jp/idenshi/research/index.html

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/idenshi/research/index.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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