2009 Fiscal Year Final Research Report
Innate immune system activation and regulation via DNA receptors.
| Project/Area Number |
19209016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TANIGUCHI Tadatsugu The University of Tokyo, 大学院・医学系研究科, 教授 (50133616)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Hideyuki 東京大学, 大学院・医学系研究科, 助教 (70431765)
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| Project Period (FY) |
2007 – 2009
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| 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 |
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| 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.
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[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.
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Journal Title
Nature Vol. 462
Pages: 99-103
Peer Reviewed
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[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.
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Journal Title
Proc.Natl.Acad.Sci.USA Vol. 106
Pages: 17870-17875
Peer Reviewed
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[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.
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Journal Title
Cancer Sci. Vol. 100
Pages: 449-456
Peer Reviewed
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[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.
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Journal Title
Proc.Natl.Acad.Sci.USA Vol. 105
Pages: 20446-20451
Peer Reviewed
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[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.
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Journal Title
Proc.Natl.Acad.Sci.USA Vol. 105
Pages: 2556-2561
Peer Reviewed
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[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.
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Journal Title
Nature Vol. 448
Pages: 501-505
Peer Reviewed
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[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
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