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ウィルス抗原の提示における樹状細胞アポトーシスの免疫学的意義

Research Project

Project/Area Number 19041011
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionAkita University

Principal Investigator

樗木 俊聡  Akita University, 医学部, 教授 (50233200)

Co-Investigator(Kenkyū-buntansha) 佐藤 卓  東北大学, 医学部, 教授 (40375259)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2008: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2007: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsDC / poly I : C / I型IFN / NOD1 / NOD2 / クロスプライミング / 自然免疫 / TLR7 / TLR9 / TRAIL / DR5 / インフルエンザウィルス
Research Abstract

本年度も、引き続き活性化DCのアポトーシス誘導機構に関わる分子基盤を明らかにすること、さらに新たなDCによるクロスプライミング誘導機構を探求することを目的として研究を行い、以下のことを明らかにした。
1. TLRリガンドによるDCアポトーシス誘導機構
合成dsRNAであるpoly I : Cを野生型マウスに投与してDCサブセットごとにアポトーシスの誘導を検討したところ、cDC、pDC共にアポトーシスの誘導が認められた。さらに誘導機序を検討したところ、特にpDCでcaspase 8の発現誘導が顕著であった。またI型インターフェロン(IFN)受容体欠損マウスではDCのアポトーシスがほぼ完全に抑制された。これらの結果から、poly I : CによるDCアポトーシスにはcaspaseとI型IFN依存性であることが示唆された。
2. DCによるクロスプライミング誘導機構
クロスプライミングによるCTLの活性化は、ウィルス感染細胞や癌細胞の排除に重要である。TLRシグナルがDCによるクロスプライミングを亢進させることは知られているが、NODシグナルの役割は不明である。本年度の研究から、1) NODIおよびNOD2リガンド刺激(NODシグナル)が、主としてCD8^+DCサブセット依存性のクロスプライミングを亢進させること、2) その機序として、MHCクラス1依存性抗原提示能および共刺激分子発現レベルが亢進することを明らかにした。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (50 results)

All 2009 2008 2007 Other

All Journal Article (19 results) (of which Peer Reviewed: 11 results) Presentation (27 results) Book (2 results) Remarks (2 results)

  • [Journal Article] IRF-2 protects quiescent HSCs from type-I interferon-dependent exhaustion2009

    • Author(s)
      Sato, T.
    • Journal Title

      Nature Medicine (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MHC-matched corneal allograft rejection in an IFN-gamma/IL-17-independentmanner in C57BL/6 mice2009

    • Author(s)
      Yamada, J.
    • Journal Title

      Invest. Ophth. Vis. Sci 50

      Pages: 2139-2146

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-15 serves as a costimulator in determining the activity of autoreactive CD8T cells in an experimental mouse model of graft-versus-host-like disease2008

    • Author(s)
      Miyagawa, F.
    • Journal Title

      J. Immunol. 181

      Pages: 1109-1119

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten inmacrophages2008

    • Author(s)
      Kuroda, S.
    • Journal Title

      Eur. J. Immunol 38

      Pages: 1331-1340

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4^+ self-reactive T cells2008

    • Author(s)
      Terme, M.
    • Journal Title

      J. Immunol 180

      Pages: 4679-4686

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 樹状細胞によるTh分化制御2008

    • Author(s)
      小内伸幸
    • Journal Title

      分子細胞治療 7

      Pages: 58-66

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 腸管における樹状細胞のトラフィッキングとIgA生産誘導機構2008

    • Author(s)
      手塚裕之
    • Journal Title

      臨床免疫・アレルギー科 49

      Pages: 10-15

    • Related Report
      2008 Annual Research Report
  • [Journal Article] IgAクラススイッチを誘導するバイエル板樹状細胞2008

    • Author(s)
      手塚裕之
    • Journal Title

      臨床免疫・アレルギー科 50

      Pages: 216-221

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 腸管粘膜樹状細胞によるIgAクラススイッチ制御-腸内常在菌の役割2008

    • Author(s)
      手塚裕之
    • Journal Title

      医学のあゆみ 227

      Pages: 326-331

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 腸管でのIgA生産を司るTNF/iNos生産性樹状細胞とその機能2008

    • Author(s)
      手塚裕之
    • Journal Title

      生体の科学 59

      Pages: 268-274

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 消化管粘膜での免疫応答における樹状細胞の1役割-小腸粘膜樹状細胞によるIgAクラススイッチ制御2008

    • Author(s)
      手塚裕之
    • Journal Title

      実験医学 26

      Pages: 3236-3242

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 樹状細胞によるIgA生産誘導機構の新知見2008

    • Author(s)
      樗木俊聡
    • Journal Title

      炎症と免疫 16

      Pages: 209-214

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 粘膜樹状細胞によるIgAクラススイッチ誘導機構2008

    • Author(s)
      安部由紀子
    • Journal Title

      感染・炎症・免疫 38

      Pages: 271-273

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages.2008

    • Author(s)
      Kuroda, S.
    • Journal Title

      Eur. J. Immunol. 38

      Pages: 1331-1340

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T Cells Control Dendritic Cell/NK Cell Cross-Talk in Lymph Nodes at the Steady State by Inhibiting CD4+Self-Reavtive T Cells.2008

    • Author(s)
      Terme, M.
    • Journal Title

      J. Immunol. 180

      Pages: 4679-4686

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of clonogenic common Flt3^+M-CSFR^+ Plasmacytoid and dendritic cell progenitors in mouse bone marrow.2007

    • Author(s)
      Onai, N.
    • Journal Title

      Nat. Immunol. 8

      Pages: 1207-1216

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells.2007

    • Author(s)
      Tezuka, H.
    • Journal Title

      Nature 448

      Pages: 929-933

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Pten/PI3K Pathway governs the homeostasis of Valphal4iNKT cells.2007

    • Author(s)
      Kishimoto, H.・Ohteki, T., (equal contribution)
    • Journal Title

      Blood 109

      Pages: 3316-3324

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The dynamics of dendritic cell-mediated innate immune regulation.2007

    • Author(s)
      Ohteki, T.
    • Journal Title

      Allergy International 56

      Pages: 209-214

    • NAID

      10019815295

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mechanisms of IgA production in the mucosa-associated lymphoid tissue2009

    • Author(s)
      樗木俊聡
    • Organizer
      第3回JSI-RCAI免疫ワークショップ「粘膜免疫機構の制御と破綻-粘膜免疫における基礎と臨床の対話-」
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      2009-03-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of IgA production by natural ly occurring TNF/INOS-producing dendritic cells2009

    • Author(s)
      Tezuka, H.
    • Organizer
      The 4th Stage Surface Barrier Immunology Study Group (SBARIS) 1_<st> Meeting「Immune Response at Mucosal Surface」
    • Place of Presentation
      Tokyo
    • Year and Date
      2009-03-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Proliferation and exhausion of HSCs by type-1 interferon2009

    • Author(s)
      Ohteki, T.
    • Organizer
      第8回日本再生医療学会総会, シンポジウムStem Cell Niche
    • Place of Presentation
      東京(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo2008

    • Author(s)
      Asano, J.
    • Organizer
      The 8th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of mucosal IgA production by dendritec cell2008

    • Author(s)
      Ohteki, T.
    • Organizer
      The 10th International Symposium on Dendritic Cells
    • Place of Presentation
      Kobe, Japan(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo2008

    • Author(s)
      Asano, J.
    • Organizer
      The 10th International Symposium on Dendritic Cells
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular mechanism of DC production of IL-15 upon CpG stimulation in vivo2008

    • Author(s)
      Fujioka, Y.
    • Organizer
      The 10th International Symposium on Dendritic Cells
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of mucosal IgA production by dendritic cells2008

    • Author(s)
      Ohteki, T.
    • Organizer
      The 2^<nd> International Symposium of WPI-IFReC"Dynamics of Immune Responses"
    • Place of Presentation
      Osaka, Japan(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of mucosal IgA production by dendritic cells2008

    • Author(s)
      Ohteki, T.
    • Organizer
      第38日本免疫学会学術集会Simposium 5 Dendritic cell
    • Place of Presentation
      京都(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] The role of hematopoietic cytokine in dendritic cell subsets development2008

    • Author(s)
      Onai, N.
    • Organizer
      第38日本免疫学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] Critical role for pDCs in mucosal T cell-independent IgA production2008

    • Author(s)
      Tezuka, H.
    • Organizer
      第38日本免疫学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] IRF-2 protects haematopoietic stem cells from type-I interferon-dependent renlicative exhaustion2008

    • Author(s)
      Sato, T.
    • Organizer
      第38日本免疫学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo2008

    • Author(s)
      Asano, J.
    • Organizer
      第38日本免疫学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular mechanism of IL-15 production from DC upon CpG stimulation in vivo2008

    • Author(s)
      Kuwajima, S.
    • Organizer
      第38日本免疫学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] 腸管粘膜組織におけるIgA生産調節機構2008

    • Author(s)
      樗木俊聡
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム「血球細胞の分化系譜」
    • Place of Presentation
      神戸(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nucleotide-binding oligomerization domain(Nod)シグナルによるDCクロスプライミングの増強効果2008

    • Author(s)
      浅野純平
    • Organizer
      第18回Kyoto T Cell Confbrence
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] 粘膜免疫系を支配するガス2008

    • Author(s)
      樗木俊聡
    • Organizer
      第32回阿蘇シンポジウム
    • Place of Presentation
      阿蘇(招待講演)
    • Related Report
      2008 Annual Research Report
  • [Presentation] Limited role of denderitic cells in the maintenance of memory CD8+T cells in lymphoreplete host.2007

    • Author(s)
      Sato, T.
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] 樹状細胞による免疫調節ダイナミズム研究2007

    • Author(s)
      樗木俊聡
    • Organizer
      第37回日本免疫学会・第10回日本免疫学会賞受賞者講演
    • Place of Presentation
      東京
    • Year and Date
      2007-11-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] pDC-derived interferon-α downregulatesTLR7-mediated immune responses through DC apoptosis.2007

    • Author(s)
      Kuwajima, S.
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 樹状細胞による粘膜免疫調節機構2007

    • Author(s)
      樗木俊聡
    • Organizer
      第3回東北内分泌研究会総会(第15回日本内分泌学会東北地方会)
    • Place of Presentation
      秋田
    • Year and Date
      2007-10-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] IgA生産調節メカニズムの新知見.2007

    • Author(s)
      樗木俊聡
    • Organizer
      歯科基礎医学会シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2007-08-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis.2007

    • Author(s)
      Ohteki, T.
    • Organizer
      International Symposium on Molecular Cell Biology of Macrophages 2007
    • Place of Presentation
      静岡
    • Related Report
      2007 Annual Research Report
  • [Presentation] Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells.2007

    • Author(s)
      Ohteki, T.
    • Organizer
      The Korean Association of Immrnobiologies 55th Fall Conference
    • Place of Presentation
      ソウル(韓国)
    • Related Report
      2007 Annual Research Report
  • [Presentation] 形質細胞様樹状細胞の生産するIFN-αによる新規免疫制御機構.2007

    • Author(s)
      樗木俊聡
    • Organizer
      第18回樹状細胞研究会
    • Place of Presentation
      淡路
    • Related Report
      2007 Annual Research Report
  • [Presentation] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis.2007

    • Author(s)
      Kuwajima, S.
    • Organizer
      第7回あわじしま感染症・免疫フォーラム
    • Place of Presentation
      淡路
    • Related Report
      2007 Annual Research Report
  • [Presentation] メモリーCD8T細胞の数的・機能的維持における樹状細胞の役割.2007

    • Author(s)
      佐藤卓
    • Organizer
      第17回Kyoto T Cell Conference
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Book] 樹状細胞による免疫調節ダイナミズム(pp.125-134)谷口, 維紹・山本, 一彦(編)免疫応答と免疫病態の統合的分子理解2007

    • Author(s)
      樗木俊聡
    • Total Pages
      269
    • Publisher
      南山堂
    • Related Report
      2007 Annual Research Report
  • [Book] CpGによる樹状細胞活性化とIL-15依存性クロスーク.(pp.138-145)奥村, 康・平野, 俊夫・佐藤, 昇志(編)Annual Review免疫20082007

    • Author(s)
      桑島精一
    • Total Pages
      317
    • Publisher
      中外医学社
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://wwwmed.akita-u.ac.jp/~kisei/Default.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.akita-u.ac.jp/~kisei/Default.html

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2018-03-28  

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