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

• 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
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: (E)細胞 / TAK1 / 炎症性腸疾患 / 制御性T細胞 / ノックアウトマウス / 粘膜免疫

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
• [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] Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2 (2008)
  • Author(s): Kawagoe T. et.al.
  • Journal Title: Nat. Immunol 9 Pages: 684-691
  • Peer Reviewed
• [Journal Article] Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 (2008)
  • Author(s): Uematsu S. et.al.
  • Journal Title: Nat. Immunol 9 Pages: 767-776
  • Peer Reviewed
• [Journal Article] Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium (2008)
  • Author(s): Saiga H. et.al.
  • Journal Title: J. Immunol 181 Pages: 8521-8527
  • Peer Reviewed
• [Journal Article] Leishmania-Induced IRAK-1 Inactivation Is Mediated by SHP-1 Intera cting with an Evolutionarily Conserved KTIM Motif (2008)
  • Author(s): Abu-Dayyeh I. et.al.
  • Journal Title: PLoS Negl. Trop. Dis 2
  • Peer Reviewed
• [Journal Article] Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor. (2008)
  • Author(s): Nishimura J., et. al.
  • Journal Title: J. Immunol. 180 Pages: 4032-4039
  • Peer Reviewed
• [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
• [Journal Article] HTLV-1 Tax-induced NFκB activation is independent of Lys-63-linked-type polyu biquitination. (2007)
  • Author(s): Gohda J., et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 357 Pages: 225-230
  • Peer Reviewed
• [Journal Article] Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor-mediated immune responses but not in TCR signalng. (2007)
  • Author(s): Kawagoe T., et. al.
  • Journal Title: J. Exp. Med. 204 Pages: 1013-1024
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Tribl deficiency. (2007)
  • Author(s): Yamamoto M., et. al.
  • Journal Title: J. Exp. Med. 204 Pages: 2233-2239
  • Peer Reviewed