Role of a nuclear protein IκBζ in innate immunity

• Project/Area Number: 21790467
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: YAMAMOTO Masahiro Osaka University, 医学系研究科, 准教授 (00444521)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 原虫 / 自然免疫学 / 遺伝学 / 核内タンパク質 / 自然免疫 / 自己免疫疾患 / T細胞分化

Research Abstract

We clarified that an nuclear IκB family protein IκBζ is a master transcriptional factor for the generation of mouse Th17 cells. Ectopic co-expression of IκBζ and RORγt strongly induced Th17 differentiation even in the absence of IL-6 and TGF-β. In addition, IκBζ-deficient mice showed defective Th17 differentiation in vivo and resistance to EAE induction. Moreover, IκBζ in collaboration with RORγt directly associated with the promoter of IL17a and highly induced expression of IL17a.

Research Products

• [Journal Article] IkBz regulates Th17 development by cooperating with ROR nuclear receptors. (2010)
  • Author(s): Okamoto K, Iwai Y, Oh-hora M, Yamamoto M, et al.
  • Journal Title: Nature. 464 Pages: 1381-5
  • Peer Reviewed
• [Journal Article] IkBz regulates Th17 development by cooperating with ROR nuclear receptors. Nature. (2010)
  • Author(s): Okamoto K, Iwai Y, Oh-hora M, Yamamoto M, et al.
  • Journal Title: Nature. Volume: 464 Pages: 1381-1385
  • Peer Reviewed
• [Journal Article] Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10. (2010)
  • Author(s): Ueda Y, Kayama H, Jeon SG, Kusu T, Isaka Y, Rakugi H, Yamamoto M, Takeda K.
  • Journal Title: Int Immunol. Volume: 22 Pages: 953-62
  • Peer Reviewed
• [Journal Article] Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice. (2010)
  • Author(s): Burkhardt R, Toh SA, Lagor WR, Birkeland A, Levin M, Li X, Robblee M, Fedorov VD, Yamamoto M, Satoh T, Akira S, Kathiresan S, Breslow JL, Rader DJ.
  • Journal Title: J Clin Invest. Volume: 120 Pages: 4410-4
  • Peer Reviewed
• [Journal Article] IkBz regulates Th17 development by cooperating with ROR nuclear receptors. Nature. (2010)
  • Author(s): Okamoto K, Iwai Y, Oh-hora M, Yamamoto M, et al.
  • Journal Title: Nature. (印刷中)
  • Peer Reviewed
• [Journal Article] Toll-like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar Typhimurium infection, but not for the initiation of bacterial clearance. (2009)
  • Author(s): Talbot S, T6temeyer S, Yamamoto M, et al.
  • Journal Title: Immunology 128 Pages: 472-83
  • Peer Reviewed
• [Journal Article] Regulation of hematopoiesis by the K63-specificubiquitin-conjugating enzyme Ubc13. (2009)
  • Author(s): Wu X, Yamamoto M, et al.
  • Journal Title: Proc Natl Acad Sci USA. 106 Pages: 20836-41
  • Peer Reviewed
• [Journal Article] A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3. (2009)
  • Author(s): Yamamoto M, et al.
  • Journal Title: J Exp Med. 206 Pages: 2747-2760
  • Peer Reviewed
• [Journal Article] Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling. (2009)
  • Author(s): Yamazaki K, Gohda J, Kanayama A, Miyamoto Y, Sakurai H, Yamamoto M, et al.
  • Journal Title: Sci Signal. 2
  • Peer Reviewed
• [Journal Article] NFATcl mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection. (2009)
  • Author(s): Kayama H, Koga R, Atarashi K, Okuyama M, Kimura T, Mak TW, Uematsu S, Akira S, Takayanagi H, Honda K, Yamamoto M, Takeda K.
  • Journal Title: PLoS Pathog. 5
  • Peer Reviewed
• [Journal Article] TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and -independent humoral immune responses. (2009)
  • Author(s): Kobayashi T, Kim TS, Jacob A, Walsh MC, Kadono Y, Fuentes-Panana E, Yoshioka T, Yoshimura A, Yamamoto M, et al.
  • Journal Title: PLoS One. 4
  • Peer Reviewed
• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-κB activation. (2009)
  • Author(s): Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, Yamamoto M, et al
  • Journal Title: Nat Cell Biol. 11 Pages: 123-32
  • Peer Reviewed
• [Journal Article] A single polymorphic amino acid on Toxoplasma gondii kinase ROP 16 determines the direct and strain-specific activation of Stat3. (2009)
  • Author(s): Yamamoto M, et al.
  • Journal Title: J Exp Med. 206 Pages: 2747-2760
  • Peer Reviewed
• [Presentation] I型トキソプラズマ原虫の病原性におけるROP18の役割 (2010)
  • Author(s): 山本雅裕
  • Organizer: 第9回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 長崎大学坂本キャンパス良順会館ボードインホール
• [Presentation] トキソプラズマ原虫リン酸化酵素ROP16による宿主自然免疫系の制御について (2010)
  • Author(s): 山本雅裕
  • Organizer: 第62回細胞生物学会、シンポジウム4(S4)感染症と細胞生物学のインターフェース
  • Place of Presentation: グランキューブ大阪(招待講演)
• [Presentation] Essential role of ROP16 in the strain-specific and direct activation of Stat3 and Stat6 (2010)
  • Author(s): Masahiro Yamamoto
  • Organizer: The 4^<th> International Symposium of WPI-IFReC
  • Place of Presentation: Icho-Kaikan, Suita Campus, Osaka University(招待講演)
• [Presentation] トキソプラズマ原虫のキナーゼであるROP16上の多型的な1つのアミノ酸置換が株特異的かつ直接的なStat3のリン酸化を決定する (2009)
  • Author(s): Yamamoto M, Soldati-Favre D, Takeda K.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] A single polymorphic amino substitution on Toxoplasma gondii kinase ROP16 detemines the direct and strain-specific activation of Stat3. (2009)
  • Author(s): Yamamoto M.
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
• [Presentation] トキソプラズマ原虫のリン酸化酵素であるROP16はStat3を直接活性化する (2009)
  • Author(s): 山本雅裕、Dominiquie Soldati-Favre, 竹田潔
  • Organizer: 第8回分子寄生虫・マラリア研究フォーラム
  • Place of Presentation: 千里ライフサイエンスセンター
• [Presentation] Essential role of Toxoplasma gondii ROP16 in host Stat3 activation (2009)
  • Author(s): Yamamoto M, Soldati-Favre D, Takeda K.
  • Organizer: The 9^<th> Awaji International Forum on lnfection and Immunity(Awaji Yumebutai Intemational Conference Center on Awaji Island
  • Place of Presentation: Hyogo, Japan
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto-accomp.pdf
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto-accomp.pdf