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新規マクロファージ亜群の同定とその生体内自己免疫反応制御における意義

Publicly Offered Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 22021003
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

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

Principal Investigator

上出 利光  北海道大学, 遺伝子病制御研究所, 教授 (00160185)

Co-Investigator(Kenkyū-buntansha) 森本 純子  北海道大学, 遺伝子病制御研究所, 助教 (20451396)
黒滝 大翼  横浜市立大学, 大学院・医学研究科, 助教 (10568455)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2011: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2010: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsマクロファージ / CSF-1 / TGF-β / Treg / インテグリン
Research Abstract

脾臓には生体のホメオスターシスを維持する為に様々な機能を有するマクロファージ(MΦ)サブセットが存在する。赤脾髄MΦ、老化した赤血球や血中の抗原を貪食する。老化赤血球は一種の自己抗原であるため、赤血球を取り込んだマクロファージが免疫反応を惹起するのは生体にとって危険である。赤脾髄には、F4/80hiMac-1lowMΦが存在するが、脾臓での主たるMΦであるF4/80hiMac-1low MΦと異なり、α9インテグリンを高発現し、炎症性ケモカイン受容体CCR2の発現は無い。F4/80hiMac-1low MΦはLPSや非メチル化CpGDNAモチーフを含むDNA配列(CpGDNA)/TLR9リガンドの刺激により炎症性サイトカインであるIL-6やIL-12p40を産生増強する。一方、F4/80hiMac-1lowMΦは、同様の刺激でIL-10の産生増強をしめした。更に恒常的に抑制性サイトカインであるTGF-βを大量に産生する。F4/80hiMac-1low MΦは抗原存在下で、樹状細胞(DC)と同等の強いヘルパーT細胞増殖を誘導するが、F4/80hiMac-1lowMΦはT細胞の増殖誘導やエフェクターサイトカインであるIFN-γの産生誘導を惹起する能力が欠如していた。T細胞の増殖は抗TGF-β抗体添加により有意に回復する事から、T細胞増殖の抑制は、恒常的に産生されるTGF-βによると判明した。2D2T細胞を抗原存在下で、F4/80hiMac-1lowMΦと培養するとFoxp3陽性regulatory T cellが誘導され、ヘルパーT細胞の増殖を抑制する事が判明した。赤脾髄MΦには、colony-stimulating factor-1(CSF-1)に依存性および非依存性の細胞が存在するが、F4/80hiMac-1lowMΦの分化、産生はCSF-1依存的であった。

Report

(2 results)
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (26 results)

All 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (17 results) Book (1 results)

  • [Journal Article] Alpha9beta1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation2011

    • Author(s)
      Kanayama M
    • Journal Title

      J.Immunol

      Volume: 187 Pages: 5851-5864

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteopontin modulates the generation of memory CD8+T cells during influenza virus infection2011

    • Author(s)
      Morimoto J
    • Journal Title

      J.Immunol

      Volume: 187 Pages: 5671-5683

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crucial role of the cryptic epitope SLAYGLR within osteopontinin renal crystal formation of mice2011

    • Author(s)
      Hamamoto S, Yasui T, Okada A, Hirose M, Matsui Y, Kon S, Sakai F, Kojima Y, Hayashi Y, Tozawa K, Uede T, Ko- hri K
    • Journal Title

      J Bone Miner Res

      Volume: 26 Issue: 12 Pages: 2967-77

    • DOI

      10.1002/jbmr.495

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CSF-1-dependent red pulp macrophages regulate CD4 T cell responses2011

    • Author(s)
      Kurotaki D
    • Journal Title

      J.Immunol

      Volume: 186 Pages: 2229-2237

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NMR characterization of intramolecular interaction of osteopontin, an intrinsically disordered protein with cryptic integrin-binding motifs.2010

    • Author(s)
      Y.Yamaguchi
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 393 Pages: 487-491

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Osteopontin Reduces Liver Metastasis of Human Pancreatic Cancer Xenografts Injected into the Spleen in a Mouse Model.2010

    • Author(s)
      K.Ohno
    • Journal Title

      Surgery Today.

      Volume: 40 Pages: 347-356

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of interaction of alpha9 integrin with its ligands hinders the formation of granulation in cutaneous wound healing.2010

    • Author(s)
      Nakayama Y
    • Journal Title

      Lab Invest.

      Volume: 90(6) Pages: 881-894

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical function of death-associated protein 3 in T cell receptor-mediated apoptosis induction.2010

    • Author(s)
      Tosa N
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 395(3) Pages: 356-360

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 細胞感染時の生体防御反応におけるリンパ節CD169陽性髄質マクロファージの役割解明2011

    • Author(s)
      黒滝大翼
    • Organizer
      第22回日本生体防御学会学術総会
    • Place of Presentation
      那覇市ぶんかテンブス館(沖縄県)
    • Year and Date
      2011-07-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] Matricellular proteins and their integrin receptors-new drug targets for inflammatory disorders and cancers2010

    • Author(s)
      上出利光
    • Organizer
      Novo Nordisk Symposium
    • Place of Presentation
      Nova Nordisk(北京市・中国)(招待講演)
    • Year and Date
      2010-11-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Osteopontin, a key intrinsic regulator of various intractable inflammatory disorders.2010

    • Author(s)
      上出利光
    • Organizer
      浙江大学講演会
    • Place of Presentation
      浙江大学(杭州市・中国)(招待講演)
    • Year and Date
      2010-06-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of Syndecan-4 in neointimal hyperplasia and atherosclerosis.2010

    • Author(s)
      Masahiro Ikesue
    • Organizer
      AHA's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference
    • Place of Presentation
      Hilton Union Square(サンフランシスコ・USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Interleukin-17 Deficiency Accelerates Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice.2010

    • Author(s)
      Keiko Danzaki
    • Organizer
      AHA's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference
    • Place of Presentation
      Hilton Union Square(サンフランシスコ・USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 組織微小環境の内的調節因子、オステオポンチンの病態病理学2010

    • Author(s)
      上出利光
    • Organizer
      第99回日本病理学会総会宿題報告
    • Place of Presentation
      京王プラザホテル(東京都)(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 心筋梗塞におけるSyndecan4の機能解析2010

    • Author(s)
      松井裕
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 実験的自己免疫性脳脊髄炎におけるα9インテグリンの機能解析2010

    • Author(s)
      伊藤甲雄
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] α9インテグリンは滑膜細胞の炎症促進的な機能を制御する2010

    • Author(s)
      金山剛士
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] brogation of integrin α9β1-mediated signaling skews the generation of functional Th17 cells in regional lymph nodes of arthritic mice.2010

    • Author(s)
      Masashi Kanayama
    • Organizer
      97^<th> Annual Meeting the American Association of Immunologists
    • Place of Presentation
      Baltimore Convention Center(ボルチモア・USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] リンパ管内皮細胞上のα9インテグリンはリンパ管リンパ節からの細胞の移出を調整する2010

    • Author(s)
      Koyu Ito
    • Organizer
      ゴードンリサーチカンファランス
    • Place of Presentation
      IL Ciocco Hotel and Resort(ルッカ・イタリア)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 動脈硬化の進展におけるInterleukin-17Aの役割の検討2010

    • Author(s)
      檀崎敬子
    • Organizer
      第21回日本生体防御学会学術総会
    • Place of Presentation
      仙台市戦災復興記念館(仙台市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] The aberrant interaction of matricellular proteins and integrins in pathological foci leads to inflammatory tissue damage.2010

    • Author(s)
      上出利光
    • Organizer
      FASEB summer research conferences
    • Place of Presentation
      The Steamboat Grand Resort(スティームボート・USA)(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Alpha9 integrin is involved in the development of experimental autoimmune encephalomyelitis by regulating cell migration from lymph node.2010

    • Author(s)
      Koyu Ito
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] α9β1 integrin regulates the generation and egress of pathoge-nic Th17 cells in autoimmune arthritis.2010

    • Author(s)
      Masashi Kanayama
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸国際展示場(神戸市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of Syndecan-4 in Neointimal Hyperplasia and Atherosclerosis.2010

    • Author(s)
      Masahiro Ikesue
    • Organizer
      American Heart Association soientific sessions
    • Place of Presentation
      McCormick Place Convention Center(シカゴ・USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] The role of osteopontin in the generation of virus-specific memory CD8T cells.2010

    • Author(s)
      Junko Morimoto
    • Organizer
      Cell Symposia
    • Place of Presentation
      Washington Marriott Hotel(ワシントン・USA)
    • Related Report
      2010 Annual Research Report
  • [Book] 医科免疫学2010(改訂第6版)2010

    • Author(s)
      上出利光
    • Total Pages
      494
    • Publisher
      南江堂
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2018-03-28  

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