Analysis of colitis shown in T cell-specific TAK1-deficient mice

2008 Fiscal Year Final Research Report

• Project/Area Number: 19790355
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: SATO Shintaro The University of Tokyo, 医科学研究所, 助教 (80447333)
• Project Period (FY): 2007 – 2008
• Keywords: (E)細胞

Research Abstract

T細胞特異的TAK1欠損マウスは自然発生的に大腸炎を発症する。TNF刺激に対する応答性の亢進が認められることから、このマウスが示す表現型がTNFの二重欠損(DKO)で回避されるかを検討したが、T細胞分化の異常や腸炎の発症はDKOマウスでも認められた。このマウスの腸炎発症にはナチュラルレギュラトリーT(nTreg)細胞の選択的欠失が関与していることが示唆されていたが、野生型マウスより調整した末梢Treg細胞の移入による腸炎発症の回避認められなかった。これらの結果は、胸腺でのCreによるTak1遺伝子の消失を逃れた未熟なT細胞亜集団が末梢で増殖することが腸炎の引き金になっていることを示唆している。

Research Products

• [Journal Article] レギュラトリーT細胞の分化とTAK1 (2009)
  • Author(s): 佐藤慎太郎
  • Journal Title: 臨床免疫・アレルギー科 51 Pages: 7-11
• [Journal Article] Leishmania-Induced IRAK-1 Inactivation Is Mediated by SHP-1 Interacting with an Evolutionarily Conserved KTIM Motif. (2008)
  • Author(s): Abu-Dayyeh I, Shio MT, Sato S, Akira S, Cousineau B, Olivier M.
  • Journal Title: PLoS. Negl. Trop. Dis. 2 Pages: e305
• [Journal Article] Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium. (2008)
  • Author(s): Saiga H, Nishimura J, Kuwata H, Okuyama M, Matsumoto S, Sato S, Matsumoto M, Akira S, Yoshikai Y, Honda K, Yamamoto M, Takeda K.
  • Journal Title: J. Immunol. 181 Pages: 8521-8527
• [Journal Article] Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. (2008)
  • Author(s): Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S.
  • Journal Title: Nat. Immunol. 9 Pages: 769-776
• [Journal Article] Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2. (2008)
  • Author(s): Kawagoe T, Sato S, Matsushita K, Kato H, Matsui K, Kumagai Y, Saitoh T, Kawai T, Takeuchi O, Akira S.
  • Journal Title: Nat. Immunol. 9 Pages: 684-691
• [Journal Article] Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor. (2008)
  • Author(s): Nishimura J, Saiga H, Sato S, Okuyama M, Kayama H, Kuwata H, Matsumoto S, Nishida T, Sawa Y, Akira S, Yoshikai Y, Yamamoto M, Takeda K.
  • Journal Title: J. Immunol. 180 Pages: 4032-4039
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency. (2007)
  • Author(s): Yamamoto M, Uematsu S, Okamoto T, Matsuura Y, Sato S, Kumar H, Satoh T, Saitoh T, Takeda K, Ishii KJ, Takeuchi O, Kawai T, Akira S.
  • Journal Title: J. Exp. Med. 204 Pages: 2233-2239
• [Journal Article] Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signaling. (2007)
  • Author(s): Kawagoe T, Sato S, Jung A, Yamamoto M, Matsui K, Kato H, Uematsu S, Takeuchi O, Akira S.
  • Journal Title: J. Exp. Med. 204 Pages: 1013-1024
• [Journal Article] HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination. (2007)
  • Author(s): Gohda J, Irisawa M, Tanaka Y, Sato S, Ohtani K, Fujisawa JI, Inoue JI.
  • Journal Title: Biochem. Biophys. Res. Commun. 25 357(1) Pages: 225-230