Regulation of mucosal immunity and homeostasis by epithelial cells and dendritic cells

• Project/Area Number: 23590933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: HIRATA YOSHIHIRO 東京大学, 医学部附属病院, 助教 (10529192)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Motoyuki 東京大学, 医学部附属病院, 助教 (90518945) ; YAMADA Atsuo 東京大学, 医学部附属病院, 助教 (80534932)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 免疫 / シグナル伝達 / 腸内細菌 / 微生物 / 免疫学

Research Abstract

The aim of this study was to understand the roles of epithelial cell and dendritic cell in the regulation of immune responses and homeostasis in colon. Epithelial cell-specific IKK knockout mice showed comparable inflammatory responses to WT mice in Citrobacter-induced colitis. In contrast, hematopoietic IKK signals are critical to mucosal accumulation of dendritic cells and regulation of Citrobacter. Dendritic cell-specific TGFbR2 knockout mice showed severe gastrointestinal inflammation and died before 12 week. Dendritic cell-specific TGFbR2 heterozygote mice also exhibited susceptibility to Citrobacter-induced colitis. The results in this study indicate TGFb signaling on dendritic cells is an important regulator of colonic homeostasis by sensing and regulating microbiota of colon.

Research Products

• [Journal Article] 自然免疫と腸炎関連大腸癌発生メカニズム (2012)
  • Author(s): 早河翼, 平田喜裕
  • Journal Title: 医学のあゆみ Volume: 241巻,3号 Pages: 202-206
• [Presentation] Transforming Growth Factor-βon dendritic cells regulates bacterial communities and gut homeostasis (2014)
  • Author(s): 井原聡三郎, 平田喜裕
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: Chicago USA
  • Year and Date: 2014-05-05
• [Presentation] 樹状細胞のTGF-betaシグナルによる腸内細菌叢の恒常性維持 (2014)
  • Author(s): 井原聡三郎, 平田喜裕
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
• [Presentation] The role of transforming growth factor-beta signaling on dendritic cells in the development of murine colitis (2013)
  • Author(s): 井原聡三郎, 平田喜裕
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: Orland USA
  • Year and Date: 2013-05-18
• [Presentation] 細菌認識機構と腸管の炎症におけるNF-kBシグナルの役割 (2011)
  • Author(s): 平田喜裕
  • Organizer: 第96回消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] The role of transforming growth factor-beta signaling on dendritic cells in the development of murine colitis
  • Author(s): 井原聡三郎
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: Orland, USA
• [Presentation] 樹状細胞のTGF-betaシグナルによる腸内細菌叢の恒常性維持
  • Author(s): 井原聡三郎
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京
• [Presentation] TGF-beta signaling on denddritic cells regulates bacterial communities and gut homeostasis
  • Author(s): 井原聡三郎
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: Chicago, USA