Analysis of the mechanisms for innate immune responses to microbes

• Project/Area Number: 19790357
• 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, 助教授 (00444521)
• 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: TLR / シグナル伝達経路 / シグナル伝達 / 転写因子 / 原虫感染免疫 / IFN-γ

Research Abstract

Toll 様受容体(TLR)シグナル伝達の負の制御因子として、ユビキチン関連分子Trib1 を同定した。Trib1 を欠損するマウスを作製したところ、Trib1 欠損細胞においてTLR 刺激による炎症性サイトカインのうちIL-12p40の産生が亢進していることを見出した。また、Trib1 欠損マウス由来の細胞においては、炎症促進転写因子であるC/EBP のタンパク質量が増加しており、それが原因でC/EBP により制御されている遺伝子群の過剰発現が見られたことが考えられた。

Research Products

• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-kappaB 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: 123-132
  • Peer Reviewed
• [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(12) Pages: 8521-8527
  • Peer Reviewed
• [Journal Article] Role of nuclear IkappaB proteins in the regulation of host immune responses (2008)
  • Author(s): Yamamoto M, Takeda K
  • Journal Title: J Infect Chemother 14(4) Pages: 265-269
  • Peer Reviewed
• [Journal Article] ATP drives lamina propria T(H)17 cell differentiation (2008)
  • Author(s): Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K, Takeda K
  • Journal Title: Nature 455(7214) Pages: 808-812
  • Peer Reviewed
• [Journal Article] Stat6-independent tissue inflammation occurs selectively on the ocular surface and perioral skin of IkappaBzeta-/- mice (2008)
  • Author(s): Ueta M, Hamuro J, Ueda E, Katoh N, Yamamoto M, Takeda K, Akira S, Kinoshita S
  • Journal Title: Invest Ophthalmol Vis Sci 49(8) Pages: 3387-3394
  • Peer Reviewed
• [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(6) Pages: 4032-4039
  • Peer Reviewed
• [Journal Article] Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta (2008)
  • Author(s): Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H, Iba H, Matsumoto M, Honda K, Smale ST, Takeda K
  • Journal Title: J Biol Chem 283(18) Pages: 12468-12477
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly (2008)
  • Author(s): Huen MS, Huang J, Yuan J, Yamamoto M, et.al.
  • Journal Title: Mol Cell Biol 19 Pages: 6104-6112
  • Peer Reviewed
• [Journal Article] Stat6-independent tissue inflammation occurs selectively on the ocular surface and perioral skin of IkappaBzeta-/- mice (2008)
  • Author(s): Ueta M, Hamuro J, Ueda E, Katoh N, Yamamoto M, et.al.
  • Journal Title: Invest Ophthalmol Vis Sci 49 Pages: 3387-3394
  • Peer Reviewed
• [Journal Article] Gene-specific requirement of a nuclear protein, IkappaB-zeta, for promoter association of inflammatory transcription regulators (2008)
  • Author(s): Yamazaki S, Matsuo S, Muta T, Yamamoto M, et.al.
  • Journal Title: J Biol Chem 283 Pages: 32404-32411
  • Peer Reviewed
• [Journal Article] ATP drives lamina propria T(H)17 cell differentiation (2008)
  • Author(s): Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, et.al.
  • Journal Title: Nature 455 Pages: 808-812
  • Peer Reviewed
• [Journal Article] Role of nuclear IkappaB proteins in the regulation of host immune responses (2008)
  • Author(s): Yamamoto M, Takeda K.
  • Journal Title: J Infect Chemother 14 Pages: 265-269
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency (2007)
  • Author(s): Yamamoto M, et al
  • Journal Title: J Exp Med 204(9) Pages: 2233-2239
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-Il6 dependent gene expressionby Tribl deficiency. (2007)
  • Author(s): Yamamoto, M., et. al.
  • Journal Title: J ExP Med. 204 Pages: 233-2239
  • 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 signaling (2007)
  • Author(s): Kawagoe T, Sato S, Jung A, Yamamoto M, et. al.
  • Journal Title: J ExP Med. 204 Pages: 1013-1024
  • Peer Reviewed
• [Journal Article] FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. (2007)
  • Author(s): Zhande R, Dauphinee SM, Thomas JA, Yamamoto M, et. al.
  • Journal Title: Mol Cell Biol. 27 Pages: 7394-8404
  • Peer Reviewed
• [Presentation] 第二回原虫感染免疫研究会 (2009)
  • Author(s): 山本雅裕
  • Place of Presentation: 佐賀、日本
• [Presentation] Tribl is a negative regulator of NF-IL6 in TLR signalling (2008)
  • Author(s): Masahiro Yamamoto
  • Organizer: Keystone Symposia, Innate Immunity
  • Place of Presentation: Keystone 米国
  • Year and Date: 2008-02-27
• [Presentation] Trib1 is a negative regulator of NF-IL6 in TLR signaling (2008)
  • Author(s): Yamamoto M, Uematsu S, Takeda K, Kawai T, Akira S
  • Organizer: Keystone Symposia, Innate Immunity: Signaling Mechanisms
  • Place of Presentation: Keystone Resort, Keystone, Colorado
• [Presentation] Differential Regulation of Primary and Secondary Response Genes by MyD88 Pathways and IκBζ (2008)
  • Author(s): Kayama H, Ramirez-Carrozzi V, Yamamoto M, Smale S, Takeda K
  • Organizer: Keystone Symposia, Innate Immunity: Signaling Mechanisms
  • Place of Presentation: Keystone Resort, Keystone, Colorado
• [Presentation] Toll-like receptor (TLR)アダプター分子・TRIF によるTrypanosomacruzi に対する感染防御機構 (2007)
  • Author(s): 山本雅裕
  • Organizer: 第15 回分子寄生虫学ワークショップ
  • Place of Presentation: 草津セミナーハウス
• [Presentation] Stat6 independent tissue inflammation of IκBζ KO mice selective in ocular surface and perioral skin (2007)
  • Author(s): Ueta M, Hamuro J, Ueda E, Katoh N, Yamamoto M, Akira S, Kinoshita S
  • Organizer: 第37 回日本免疫学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses (2007)
  • Author(s): Kato H, Sato S, Yamamoto M, Uematsu S, Matsushita K, Jung A, Ishii K, Kawai T, Takeuchi O, Akira S
  • Organizer: 第37 回日本免疫学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] C/EBPb isoform, 34 kDa LAP is responsible for NF-IL6-mediated gene induction in activated macrophages but not essential for intracellular bacteria killing (2007)
  • Author(s): Uematsu S, Kaisho T, Tanaka T, Matsumoto M, Yamamoto M, Akira S
  • Organizer: 第37 回日本免疫学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] Critical role of mouse secretory leukocyte protease inhibitor in mycobacterial infection (2007)
  • Author(s): Nishimura J, Saiga H, Matsumoto S, Kuwata H, Yoshikai Y, Yamamoto M, Takeda K
  • Organizer: 第37 回日本免疫学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto2.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/yamamoto2.html