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Innate immune system activation and regulation via DNA receptors.

Research Project

Project/Area Number 19209016
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokyo

Principal Investigator

TANIGUCHI Tadatsugu  The University of Tokyo, 大学院・医学系研究科, 教授 (50133616)

Co-Investigator(Kenkyū-buntansha) YANAI Hideyuki  東京大学, 大学院・医学系研究科, 助教 (70431765)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2008: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2007: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
Keywords自然免疫 / 核酸認識受容体 / インターフェロン / シグナル伝達 / 遺伝子発現 / 拡散認識受容体 / 遣伝子発現
Research Abstract

Recently, we had identified a novel cytosolic DNA sensing molecule, DAI (DNA-dependent activator of IRFs). We analyzed the activating mechanism of DAI by cytosolic DNA stimulation and we found a new DNA binding domain and phosphorylation sites in DAI protein. These domain and amino acid residues are turned out to be important for DNA-mediated activation of innate immune responses. To investigate further the role of DAI in innate immune responses in vivo, we generated mice deficient in Dai gene. Dai^<-/-> mice grew normally with normal cellular population in lymphoid organs compared to those of wild-type control mice. We analyzed the role of DAI in innate immune responses and found defects in mRNA induction levels of some antiviral genes in Dai^<-/-> cells.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (56 results)

All 2010 2009 2008 2007

All Journal Article (32 results) (of which Peer Reviewed: 32 results) Presentation (22 results) Book (2 results)

  • [Journal Article] Regulation of immunity and oncogenesis by the IRF transcription factor family2010

    • Author(s)
      Savitsky D, Tamura T, Yanai H, Taniguchi T.
    • Journal Title

      Cancer Immunol.Immunother. Vol. 59

      Pages: 489-510

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of immunity and oncogenesis by the IRF transcription factor family.2010

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

      Cancer Immunol. Immunother. 59

      Pages: 489-510

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HMGB proteins function as universal sentinels for nucleic acid-mediated innate immune responses2009

    • Author(s)
      Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani R, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T.
    • Journal Title

      Nature Vol. 462

      Pages: 99-103

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA2009

    • Author(s)
      Choi MK, Wang Z, Ban T, Yanai H, Lu Y, Koshiba R, Nakaima Y, Hangai S, Savitsky D, Nakasato M, Negishi H, Takeuchi O, Honda K, Akira S, Tamura T, Taniguchi T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol. 106

      Pages: 17870-17875

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutation concomitant with the disruption of the juxtaposed Irf3 gene2009

    • Author(s)
      Nakajima A, Nishimura K, Nakaima Y, Oh T, Noguchi S, Taniguchi T, Tamura T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol. 106

      Pages: 12448-12452

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells2009

    • Author(s)
      Suzuki S, Nakasato M, Shibue T, Koshima I, Taniguchi T.
    • Journal Title

      Cancer Sci. Vol. 100

      Pages: 759-769

    • NAID

      10025144902

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role for constitutive type I interferon signaling in the prevention of cellular transformation2009

    • Author(s)
      Chen HM, Tanaka N, Mitani Y, Oda E, Nozawa H, Chen JZ, Yanai H, Negishi H, Choi MK, Iwasaki T, Yamamoto H, Taniguchi T, Takaoka A.
    • Journal Title

      Cancer Sci. Vol. 100

      Pages: 449-456

    • NAID

      10025143268

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the cytosolic DNA-sensing system in innate immunity : a current view2009

    • Author(s)
      Yanai H, Savitsky D, Tamura T, Taniguchi T.
    • Journal Title

      Curr.Opin.Immunol. Vol. 1

      Pages: 17-22

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] HMGB proteins function as universal sentinels for nucleic acid-mediated innate immune responses.2009

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

      Natrue 462

      Pages: 99-103

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA.2009

    • Author(s)
      Choi MK., et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 106

      Pages: 17870-17875

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutati on concomitant with the disruption of the juxtaposed Irf3 gene.2009

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

      Proc.Natl.Acad.Sci.USA. 106

      Pages: 12448-12452

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells.2009

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

      Cancer Sci. 100

      Pages: 759-769

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the cytosolic DNA-Sensing system in innate immunity: a current view2009

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

      Current Opinion in Immunology 21

      Pages: 17-22

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role for constitutive type I interferon signaling in the prevention of cellular transformation2009

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

      Cancer Sciencs 100

      Pages: 449-456

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells.2009

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

      Cancer Sciencs 100

      Pages: 759-769

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity2008

    • Author(s)
      Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol. 105

      Pages: 20446-20451

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules2008

    • Author(s)
      Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol. 105

      Pages: 5477-5482

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The IRF Family Transcription Factors in Immunity and Oncogenesis2008

    • Author(s)
      Tamura T, Yanai H, Savitsky D, Taniguchi T.
    • Journal Title

      Annu.Rev.Immunol. Vol. 26

      Pages: 535-584

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interferon regulatory factor family of transcription factors and regulation of oncogenesis2008

    • Author(s)
      Takaoka A, Tamura T, Taniguchi T.
    • Journal Title

      Cancer Sci. Vol. 99

      Pages: 467-478

    • NAID

      10024003254

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis2008

    • Author(s)
      Couzinet A, Tamura K, Chen HM, Nishimura K, Wang Z, Morishita Y, Takeda K, Yagita H, Yanai H, Taniguchi T, Tamura T.
    • Journal Title

      Proc.Natl.Acad.Sci.USA Vol. 105

      Pages: 2556-2561

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The contribution of transcription factor IRF1 to the interferon-gamma-interleukin12 signaling axis and T(H)1 versus T (H)-17 differentiation of CD4(+) T cells2008

    • Author(s)
      Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, Honda K, Kubo M, Taniguchi T.
    • Journal Title

      Nat.Immunol. Vol. 9

      Pages: 34-41

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity.2008

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

      Prov. Natl. Acad. Sci. USA. 105

      Pages: 20446-20451

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon regulatory factor family of transcription factors and regulation of oncogenesis2008

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

      Cancer Science 99

      Pages: 467-478

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of typeI interferon signaling2008

    • Author(s)
      Mizutani T., et. al.
    • Journal Title

      Experimental Hematology 36

      Pages: 255-264

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A cell-type-specific requirement for IFN regulatory factor 5(IRF5)in Fas-induced apoptosis2008

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

      Proceedings of National Academy of Science USA 105

      Pages: 2556-2561

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The IRF Family Transcription Factors in Immunity and Oncogenesis2008

    • Author(s)
      Tamura T., et. al.
    • Journal Title

      Annual Review of Immunology 26

      Pages: 535-584

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of innate immune responses by DAI(DLM-1/ZBP1)and other DNA-sensing molecules2008

    • Author(s)
      Wang Z., et. al.
    • Journal Title

      Proceedings of National Academy of Science USA 105

      Pages: 5477-5482

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response2007

    • Author(s)
      Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T.
    • Journal Title

      Nature Vol. 448

      Pages: 501-505

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism2007

    • Author(s)
      Onoguchi K, Yoneyama M, Takemura A, Akira S, Taniguchi T, Namiki H, Fujita T.
    • Journal Title

      J.Biol.Chem. Vol. 282

      Pages: 7576-7581

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] DAI(DLM-1/ZBP1)is a cytosolic DNA sensor and an activator of innate immune response2007

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

      Nature 448

      Pages: 501-505

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The contribution of transcription factor IRFI to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4^+T cells2007

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

      Nature Immunology 9

      Pages: 34-41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Viral infections activate types I and III interferon genes through a common mechanism2007

    • Author(s)
      Onoguchi K., et. al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 7576-7581

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Sencing signaling and transcription in the innate immune respons2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      The 6th Congress of the Chinese Society for Immunology
    • Place of Presentation
      西安(中国)
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Cytoplasmic receptors for the perception of danger2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      1st International Conference on Immunochemoth erapy
    • Place of Presentation
      パリ(フランス)
    • Year and Date
      2008-10-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of Innate Immune Responses by DAI (DLM-1/ZBP1) and Other DNA-Sensing Molucules.2008

    • Author(s)
      Wang, Z. , et al.
    • Organizer
      Cytokines 2008 - 7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2008-10-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] "30 Years After the Dawn of Cytokine Molucular Biology: Roles of IRF Transcription Factors"2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      Cytokines 2008 - 7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2008-10-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] 核酸認識による免疫系の活性化2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      Toll 2008国際会議
    • Place of Presentation
      リスボン(ポルトガル)
    • Year and Date
      2008-09-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] The IRF family transcription factors in oncogenes and immunity2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      Molecular biology of cancer: 20 years of progress punctuated by the Pezcoller Symposia
    • Place of Presentation
      トレノ(イタリア)
    • Year and Date
      2008-06-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Interferons and DNA Sensors2008

    • Author(s)
      Taniguchi T.
    • Organizer
      Perspectives in Immunology Symposium
    • Place of Presentation
      in the Timken Amphitheater, Green Hospital, in La Jolla, California, USA
    • Year and Date
      2008-05-12
    • Related Report
      2009 Final Research Report
  • [Presentation] Interferons and DNA Sensors2008

    • Author(s)
      Taniguchi, T.
    • Organizer
      Perspectives in Immunology Symposium
    • Place of Presentation
      サンディエゴ(アメリカ合衆国)
    • Year and Date
      2008-05-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Sensing,signaling and transcription in innate immune responses2008

    • Author(s)
      谷口 維紹
    • Organizer
      lst Intemational-Singapore Syposlum of Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2008-01-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] Sencing, signaling and transcription in the innate immune response2008

    • Author(s)
      Taniguchi T.
    • Organizer
      The 6th Congress of the Chinese Society for Immunology
    • Place of Presentation
      西安、中華人民共和国
    • Related Report
      2009 Final Research Report
  • [Presentation] Cytoplasmic receptors for the perception of danger2008

    • Author(s)
      Taniguchi T.
    • Organizer
      1st International Conference on Immunochemotherapy
    • Place of Presentation
      Paris, France
    • Related Report
      2009 Final Research Report
  • [Presentation] 30 Years After the Dawn of Cytokine Molecular Biology : Roles of IRF Transcription Factors2008

    • Author(s)
      Taniguchi T.
    • Organizer
      Cytokines 2008-7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
    • Place of Presentation
      モントリオール (カナダ)
    • Related Report
      2009 Final Research Report
  • [Presentation] Regulation of Innate Immune Responses by DAI (DLM-1/ZBP1) and Other DNA-semsing Molecules2008

    • Author(s)
      Wang Z., et al.
    • Organizer
      7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
    • Place of Presentation
      モントリオール (カナダ)
    • Related Report
      2009 Final Research Report
  • [Presentation] 核酸認識による免疫系の活性化2008

    • Author(s)
      Taniguchi T.
    • Organizer
      Toll 2008国際会誌
    • Place of Presentation
      Lisbon, Portugal
    • Related Report
      2009 Final Research Report
  • [Presentation] The IRF family transcription factors in oncogenes and immunity2008

    • Author(s)
      Taniguchi T.
    • Organizer
      Molecular biology of cancer : 20 years of progress punctuated by the Pezcoller Symposia
    • Place of Presentation
      in Trento, Italy
    • Related Report
      2009 Final Research Report
  • [Presentation] Senseing, signaling and transcription in innate immune responses2008

    • Author(s)
      Taniguchi T.
    • Organizer
      1st International-Singapore Symposium of Immunology
    • Place of Presentation
      Biopolis, Singapore
    • Related Report
      2009 Final Research Report
  • [Presentation] IRF-5の抗ウイルス応答及び抗腫瘍応答における役割2007

    • Author(s)
      柳井 秀元
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフイコ横浜
    • Year and Date
      2007-10-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] IRFs in Innate Immune Signaling2007

    • Author(s)
      谷口 維紹
    • Organizer
      Interacademy Symposium:innate immunity and its interface with adaptive immunity
    • Place of Presentation
      Hostellerie du Mont Sainte Odile,France
    • Year and Date
      2007-09-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] IRFs in Innate Immune Signaling2007

    • Author(s)
      Taniguchi T.
    • Organizer
      Interacademy Symposium : Innate immunity and its interface with adaptive immunity
    • Place of Presentation
      France
    • Year and Date
      2007-08-31
    • Related Report
      2009 Final Research Report
  • [Presentation] Regulation of immune response and tumor suppression by the IRF family transcription factors2007

    • Author(s)
      谷口 維紹
    • Organizer
      International Conference on Immunology
    • Place of Presentation
      上海国際会議場
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] IRF-5の抗ウイルス応答及び抗腫瘍応答における役割2007

    • Author(s)
      柳井秀元
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜 (横浜)
    • Related Report
      2009 Final Research Report
  • [Presentation] Regulation of immune response and tumor suppression by the IRF family transcription factors2007

    • Author(s)
      Taniguchi T.
    • Organizer
      International Conference on Immunology
    • Place of Presentation
      China
    • Related Report
      2009 Final Research Report
  • [Book] 免疫応答と免疫病態の統合的分子理解2007

    • Author(s)
      谷口維紹
    • Total Pages
      269
    • Publisher
      南山堂
    • Related Report
      2009 Final Research Report
  • [Book] 免疫応答と免疫病態の統合的分子理解2007

    • Author(s)
      谷口 維紹
    • Total Pages
      269
    • Publisher
      南山堂
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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