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人工脾臓の構築-脾臓の白脾髄の人工的構築

Research Project

Project/Area Number 09F09746
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Immunology
Research InstitutionKyoto University

Principal Investigator

渡邊 武  京都大学, 医学研究科, 特別研究員

Co-Investigator(Kenkyū-buntansha) TAN Jonathan Kah Hua  京都大学, 医学研究科, 外国人特別研究員
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2010: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2009: ¥600,000 (Direct Cost: ¥600,000)
Keywords人工脾臓 / 脾臓白脾髄 / ストローマ細胞 / 感染症 / 腫瘍免疫 / 再生医学
Research Abstract

本研究では体内で長期にわたり強い免疫機能を発揮できる脾臓類似のデバイスの開発をめざした。その目的でまず、マウスの系において脾臓の人工的構築を行った。脾臓内皮細胞ストローマ細胞の同定および新たな細胞株の樹立を行った。新生児(生後3日目)のマウスの脾臓から脾臓カプセル(ストローマ)細胞を調整し、脾臓を摘出した正常のadultレシピエントマウスの腎皮膜下に移植して脾臓組織誘導能があるかどうかを調べたところ、移植3-4週後に中心動脈血管のまわりにT細胞領域、その周囲にB細胞領域を持つ脾臓白脾髄組織が形成された。その構造は自然の脾臓と全く同じ構造、細胞組成であった。さらに驚くべきことに赤脾髄も完全な構造が構築できた。生後8日目の脾臓ストローマ細胞では形成能の低下が見られた。レシピエントを抗原で免疫したところ、人工的構築した脾臓においてもレシピエントの脾臓と同程度あるいはそれ以上の二次免疫反応が誘導された。生後3日目の脾臓ストローマ細胞をリンフォトキシン欠損マウスに移植したところ、脾臓の再生は起らなかった。このことから、我々の系での脾臓再生にはリンフォトキシンあるいはリンフォトキシン産生性インデューサー細胞の存在が必須であることがわかった。今後、さらに、ヒト化マウスの系を用いて人型の人工リンパ節、脾臓白皮髄の構築のための基礎的研究を行う。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (12 results)

All 2010 2009

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (1 results)

  • [Journal Article] Synthesis of tissue-engineered lymphoid tissues.2010

    • Author(s)
      Tan J., Watanabe T.
    • Journal Title

      Advances in Immunology

      Volume: 印刷中

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histamine regulation in glucose and lipid metabolism via histamine receptors : Model for nonalcoholic steatohepatitis in mice2010

    • Author(s)
      Ke-Y Wang, T.Watanabe, Y.Sasaguri, ほか
    • Journal Title

      American J.Pathology

      Volume: 198 印刷中

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintainance of basal sleep/wake states.2010

    • Author(s)
      M.Hondo, K.Nagai, K.Ohno, Y.Kisanuki, J.T.Willie, T.Watanabe, M.Yanagisawa, T.Sakurai.
    • Journal Title

      Acta Physiologica

      Volume: 198 Pages: 287-294

    • Related Report
      2010 Annual Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of antihistamines on innate immune responses to severe bacterial infection in mice.2010

    • Author(s)
      M.Metz, E.Doyle, C.B.Jensen, T.Watanabe, 他
    • Journal Title

      International Archives of Allergy and Immunology

      Volume: 155 Pages: 355-360

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated Regulatory T cells are the major T cell type emigrating from sensitized skin.2010

    • Author(s)
      M.Tomura, T.Watanabe, K.Kabashima, ほか
    • Journal Title

      J.Clin.Invest.

      Volume: 120 Pages: 883-893

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of artificial lymphoid tissues with immunological function.2010

    • Author(s)
      Kobayashi Y., T.Watanabe
    • Journal Title

      Trends in Immunology

      Volume: 31 Pages: 422-428

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of tissue-engineered lymphoid tissues.2010

    • Author(s)
      Tan J., Watanabe T..
    • Journal Title

      Advances in Immunology (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histamine regulation in glucose and lipid metabolism via histamine receptors : Model for nonalcoholic steatohepatitis in mice.2010

    • Author(s)
      Ke-Y Wang, T.Watanabe, Y.Sasaguri, ほか8名
    • Journal Title

      American J.Pathology 198(印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated Regulatory T cells are the major T cell type emigrating from sensitized skin.2010

    • Author(s)
      M.Tomura, T.Watanabe, K.Kabashima., ほか9名
    • Journal Title

      J.Clin.Invest. 120

      Pages: 883-893

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse model of disease.2009

    • Author(s)
      W.Beghdadi, T.Watanabe, H.S.Mecheri., ほか7名
    • Journal Title

      Medical Science(Paris) 25

      Pages: 377-381

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histidine decarboxylase but not histamine receptor 1 or 2 deficiency protects from K/BxN serum-induced arthritis.2009

    • Author(s)
      N.Rajasekaran, Solomon S., Watanabe T., Ohtsu H., Gajda R., Illges H
    • Journal Title

      International Immunology 21

      Pages: 1263-1268

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Generation of Artificial Lymph Nodes as a synthetic immunology.2009

    • Author(s)
      渡邊武
    • Organizer
      第2回ヨーロッパ免疫学会議
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2024-03-26  

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