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Roles of cytokines and TLRs in lymphocyte activation and differentiation

Research Project

Project/Area Number 20390141
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionUniversity of Toyama

Principal Investigator

TAKATSU Kiyoshi  University of Toyama, 大学院・医学薬学研究部(医学), 教授 (10107055)

Co-Investigator(Kenkyū-buntansha) NAGAI Yoshinori  富山大学, 大学院・医学薬学研究部(医学), 准教授 (30431761)
IKUTANI Masashi  富山大学, 大学院・医学薬学研究部(医学), 助教 (40513718)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2008: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywordsリンパ球 / IL-5 / TLR / 抗原交叉提示 / 免疫学 / 自然免疫 / IFN-γ / Iigp1
Research Abstract

To investigate IL-5-producing cells in the peripheral tissues, we succeeded to generate IL-5/GFP knock-in mice. IL-5/GFP^+ cells were distributed mainly in the lung and intestinal tissues and they were CD3^- c-kit^- cells but not CD3^+ T cells. We also analyzed RP105 signals in B cell activation and found that RP105 was required for TLR4-dependent plasma cell differentiation and IgM production. Finally, we demonstrated that an interferon-inducible gene Iigp1 had a crucial role in Th1-dependent antigen cross-presentation.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (62 results)

All 2011 2010 2009 2008 Other

All Journal Article (20 results) (of which Peer Reviewed: 18 results) Presentation (32 results) Book (6 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Local microbleeding facilitates IL-6-and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.2011

    • Author(s)
      Murakami M., Takatsu K.
    • Journal Title

      Journal of Experimental Medicine Vol.208

      Pages: 103-114

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosome containing MHC-II molecules capable of antigen presentation.2011

    • Author(s)
      Ramachandra L., Takatsu K.
    • Journal Title

      Infection and Immunity Vol.78

      Pages: 5116-5125

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing MHC-II molecules capable of antigen presentation.2011

    • Author(s)
      Murakami, M., et al.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 208 Pages: 103-114

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis.2010

    • Author(s)
      Shafiani S., Takatsu K.
    • Journal Title

      Journal of Experimental Medicine Vol.207

      Pages: 1409-1420

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppressed induction of mycobacterial antigen-specific Th1-type CD4+T cells in the lung after pulmonary mycobacterial infection.2010

    • Author(s)
      Yahagi A., Takatsu K.
    • Journal Title

      International Immunology Vol.20

      Pages: 307-318

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppressed induction of mycobacterial antigen-specific Thl-type CD4+ T cells in the lung after pulmonary mycobacterial infection.2010

    • Author(s)
      Yahagi, A., et al.
    • Journal Title

      International Immunology

      Volume: 20 Pages: 307-318

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis.2010

    • Author(s)
      Shafiani, S., et al.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 207 Pages: 1409-1420

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing MHC-II molecules capable of antigen presentation.2010

    • Author(s)
      Ramachandra, L., et al.
    • Journal Title

      Infection and Immunity

      Volume: 78 Pages: 5116-5125

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory mechanism for adipose tissue M1 and M2 macrophages in diet-induced obese mice.2009

    • Author(s)
      Fujisaka S., Ikutani M., Nagai Y., Takatsu K.
    • Journal Title

      Diabetes Vol.58

      Pages: 2574-2682

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-5 and eosinophil-mediated inflammation : from discovery to therapy.2009

    • Author(s)
      Kouro, T., Takatsu K.
    • Journal Title

      International Immunology Vol.21

      Pages: 1303-1309

    • NAID

      10027390533

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Toll-like receptor 7 cooperates with antigen receptors and CD38 for induction of class switch recombination and terminal B cell maturation.2009

    • Author(s)
      Tsukamoto Y., Nagai Y., Kaisho T., Takatsu K.
    • Journal Title

      Mol.Immunol. Vol.46

      Pages: 1276-1288

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-5と好酸球で誘導されるアレルギー性炎症2009

    • Author(s)
      長井良憲、高津聖志
    • Journal Title

      実験医学増刊号「アレルギー疾患の免疫制御」 Vol.27

      Pages: 107-113

    • Related Report
      2010 Final Research Report
  • [Journal Article] Regulatory mechanism for adipose tissue M1 and M2 macrophages in diet-induced obese mice.2009

    • Author(s)
      Fujisaka, S., et al.
    • Journal Title

      Diabetes 58

      Pages: 2574-2682

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-5- and eosinophil-mediated inflammation : from discovery to therapy.2009

    • Author(s)
      Kouro, T., Takatsu, K.
    • Journal Title

      Int.Immunol. 21

      Pages: 1303-1309

    • NAID

      10027390533

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-5と好酸球で誘導されるアレルギー性炎症2009

    • Author(s)
      長井良憲、高津聖志
    • Journal Title

      実験医学増刊「アレルギー疾患の免疫機構」 27

      Pages: 107-113

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells.2008

    • Author(s)
      Emslie D., Takatsu K.
    • Journal Title

      Journal of Experimental Medicine Vol.205

      Pages: 409-428

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokines-and integrin-mediated signals.2008

    • Author(s)
      Takizawa H., Takatsu K.
    • Journal Title

      Experimental Hematology Vol.36

      Pages: 897-906

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Participation of intracellular adhesion molecule-2 (CD102) in B lymphopoiesis2008

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

      Immunol. Lett. 120

      Pages: 79-86

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokine- and integrin-mediated signals2008

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

      Exp. Hematol. 36

      Pages: 897-906

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor alpha chain expression on activated B cells2008

    • Author(s)
      Emslie, D., et al.
    • Journal Title

      J. Exp. Med. 205

      Pages: 409-421

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Participation of Bruton's tyrosine kinase in immune response to nasal influenza vaccination.2010

    • Author(s)
      Kouro, T.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] The maintenance of gut-associated lymphoid tissues regulated by Lnk/Sh2B3 adaptor, a shared risk factor gene associated with type 1 diabetes and celiac disease.2010

    • Author(s)
      Katayama, H.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Lnk/SH2B3, a gene associated with risk of several autoimmune diseases regulates proliferaion and retinoic acid production of dendritic cells.2010

    • Author(s)
      Iwasaki, Y.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of mouse strain-dependent contact hypersensitivity : production of antigen-specific IgM antibodies by B-1 cells.2010

    • Author(s)
      Itakura, A.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] B-1 cell lineage specification occurs between hematopoietic stem cell and prolymphocyte stages by differentiation environments.2010

    • Author(s)
      Iida, R.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Final Research Report
  • [Presentation] IFN-γ-inducible GTPase regulates T cell-mediated antigen cross-presentation by antigen-presenting cells.2010

    • Author(s)
      Kariyone, A.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Final Research Report
  • [Presentation] IFN-g-inducible GTPase regulates T-cell-mediated antigen cross-presentation by antigen-presenting cells.2010

    • Author(s)
      Kariyone, A., et al.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] B-1 cell lineage specification occurs between hematopoieic stem cell and prolymphocyte stages by differentiation environments.2010

    • Author(s)
      Iida, R., et al.
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Lnk/SH2B3, a gene associated with risk of several autoimmune diseases regulates proliferation and retinoic acid production of dendritic cells.2010

    • Author(s)
      Iwasaki, Y., et al
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Year and Date
      2010-08-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular mechanisms of Th1-mediated antigen cross-presentation : roles of Iigp1 and ingenol.2010

    • Author(s)
      Kariyone, A.
    • Organizer
      The 97^<th> Annual Meeting of the American Association of Immunologists.
    • Place of Presentation
      Baltimore, Maryland
    • Year and Date
      2010-05-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular mechanisms of Th1-mediated antigen cross-presentation : roles of Iigp1 and ingenol.2010

    • Author(s)
      Kariyone, A., et al.
    • Organizer
      The 97^<th> Annual Meeting of the American Association of Immunologists
    • Place of Presentation
      Baltimore, Maryland
    • Year and Date
      2010-05-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] An adaptor protein Lnk/Sh2B3, negative regulator of lymphohematopoiesis, contributes to the maintenance of gut-associated lymphoid tissues.2009

    • Author(s)
      Katayama, H.
    • Organizer
      第39回日本免疫学会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] An adaptor protein Lnk/Sh2B3, negative regulator of lymphohematopoiesis, contributes to the maintenance of gut-associated lymphoid tissues.2009

    • Author(s)
      Katayama, H., et al.
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-12-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Phenotypic and functional analysis of unique intestinal CD3-IL-2R+ cells.2009

    • Author(s)
      Ogawa, S.
    • Organizer
      第39回日本免疫学会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-12-03
    • Related Report
      2010 Final Research Report
  • [Presentation] Phenotypic and functional analysis of unique intestinal CD3-IL-2R+cells.2009

    • Author(s)
      Ogawa, S., et al.
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Molecular basis of immune responses and inflammation : Effects of herbal natural products.2009

    • Author(s)
      Takatsu, K.
    • Organizer
      The 12^<th> International Symposium on Traditional Medicine : Establishment of scientific platform for natural medicine
    • Place of Presentation
      富山
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular basis of immune responses and inflammation : Effects of herbal natural products (Invited lecture).2009

    • Author(s)
      Takatsu, K., et al.
    • Organizer
      The 12^<th> International Symposium on Traditional Medicine : Establishment of scientific platform for natural medicine
    • Place of Presentation
      富山市
    • Year and Date
      2009-11-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] PDCA-1 and plasmacytoid dendritic cells.2009

    • Author(s)
      Nakamura, T.
    • Organizer
      The 9^<th> World Congress on Inflammation
    • Place of Presentation
      東京
    • Year and Date
      2009-07-08
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Natural plant products modulate innate immunity via TLRs.2009

    • Author(s)
      Honda, H.
    • Organizer
      The 9^<th> World Congress on Inflammation
    • Place of Presentation
      東京
    • Year and Date
      2009-07-08
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Identification of soluble MD-1 and its role in autoimmune diseases.2008

    • Author(s)
      Sasaki, S.
    • Organizer
      第38回日本免疫学会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-03
    • Related Report
      2010 Final Research Report
  • [Presentation] Identification of soluble MD-1 and its role in autoimmune diseases2008

    • Author(s)
      Sasaki, S., et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-03
    • Related Report
      2008 Annual Research Report
  • [Presentation] TLR4/MD-2 and RP105/MD-1 differentially regulate LPS responsiveness in B cells.2008

    • Author(s)
      Nagai, Y.
    • Organizer
      第38回日本免疫学会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] B-1 cell restricted differentiation of IL-7R+ lymphoid progenitors from fetal liver.2008

    • Author(s)
      Kouro, T.
    • Organizer
      第38回日本免疫学会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Regulated expression of Lnk/Sh2B3 adaptor protein in lymphohematopoietic system in the Lnk : GFP knock-in reporter mice.2008

    • Author(s)
      Katayama, H.
    • Organizer
      第38回日本免疫学会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel regulatory machinery for dendritic cell production mediated by Lnk/SH2B3, a negative regulator of lymphohematopoiesis.2008

    • Author(s)
      Iwasaki, Y.
    • Organizer
      第38回日本免疫学会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel regulatory machinery for dendritic cell production mediated by Lnk/SH2B3, a negative regulator of lymphohematopoiesis2008

    • Author(s)
      Iwasaki, Y., et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulated expression of Lnk/Sh2b3 adaptor protein in lymphohematopoietic system in the Lnk : GFP knock-inreporter mice2008

    • Author(s)
      Katayama, H., et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] B-1 cell restricted differentiation of IL-7R+ lymphoid progenitors from fetal liver2008

    • Author(s)
      Kouro, T., et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] TLR4/MD-2 and RP105/MD-1 differentially regulate LPS responsiveness in B cells2008

    • Author(s)
      Nagai, Y., et al.
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] Role of IL-5 in the immune response and inflammation.2008

    • Author(s)
      Takatsu, K.
    • Organizer
      4^<th> FIMSA Congress.
    • Place of Presentation
      Taipei, Taiwan
    • Related Report
      2010 Final Research Report
  • [Presentation] Role of IL-5 in the immune response and inflammation2008

    • Author(s)
      Takatsu, K.
    • Organizer
      4^<th> FIMSA Congress
    • Place of Presentation
      Taipei, Taiwan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Drug manufacturing and innovative drug discovery in Toyama-Search for immunoregulatory molecules.2008

    • Author(s)
      Takatsu, K.
    • Organizer
      JETRO Swiss-Japanese Business Information Seminar
    • Place of Presentation
      Geneva, Switerland
    • Related Report
      2008 Annual Research Report
  • [Book] 「免疫生物学」原著第7版(第III部 成熟リンパ球のセレプターレパートリーの発生6免疫系レセプターを介するシグナル伝達)2010

    • Author(s)
      生谷尚士、高津聖志
    • Publisher
      南江堂
    • Related Report
      2010 Final Research Report
  • [Book] 臨床粘膜免疫学(Th1/Th2/Treg細胞とサイトカインによる分泌型IgA誘導・制御機構)2010

    • Author(s)
      柳橋努、高津聖志
    • Publisher
      シナジー
    • Related Report
      2010 Final Research Report
  • [Book] 医学のあゆみ(IL-5による自然免疫制御)2010

    • Author(s)
      紅露拓、高津聖志
    • Publisher
      医学書院
    • Related Report
      2010 Final Research Report
  • [Book] 「免疫生物学」原書第7版(笹月健彦監訳)(第III部成熟リンパ球のレセプターレパートリーの発生,6免疫系レセプターを介するシグナル伝達)2010

    • Author(s)
      生谷尚士, 高津聖志
    • Total Pages
      38
    • Publisher
      南江堂
    • Related Report
      2010 Annual Research Report
  • [Book] 臨床粘膜免疫学(清野宏編集)(Th1/Th2/Treg細胞とサイトカインによる分泌型IgA誘導・制御機構)2010

    • Author(s)
      柳橋努, 高津聖志
    • Total Pages
      9
    • Publisher
      シナジー
    • Related Report
      2010 Annual Research Report
  • [Book] 医学のあゆみ,IL-5による自然免疫制御2010

    • Author(s)
      紅露拓, 高津聖志
    • Total Pages
      6
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.u-toyama.ac.jp/immbio/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.med.u-toyama.ac.jp/immbio/

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] トランスジェニック非ヒト哺乳動物およびその利用2009

    • Inventor(s)
      高津聖志、生谷尚士、高木智
    • Industrial Property Rights Holder
      富山大学、国立国際医療研究センター
    • Industrial Property Number
      2009-177159
    • Filing Date
      2009-07-30
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] トランスジェニック非ヒト哺乳動物およびその利用2009

    • Inventor(s)
      高津聖志, 生谷尚史, 高木智
    • Industrial Property Rights Holder
      富山大学国立国際医療研究センター
    • Industrial Property Number
      2009-177159
    • Filing Date
      2009-07-30
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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