The roles of PRR and cytokines in the development of intestinal microbiota-dependent inflammatory bowel diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 23700508
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Tokyo University of Science (2012); The University of Tokyo (2011)
• Principal Investigator: TANG Ce 東京理科大学, 生命医科学研究所, 助教 (00572166)
• Project Period (FY): 2010 – 2012
• Keywords: C型レクチン / 腸内細菌叢 / サイトカイン / 炎症性腸疾患 / 遺伝子欠損マウス

Research Abstract

The intestinal immune system has to take dual tasks; the system should fight against invading pathogens and, at the same time, the system should be tolerant toward commensal microbiota or food components. Dectin-1 is the receptor for beta-glucans expressed in fungal cell walls and activates the immune system toprevent infection. Because beta-glucans are contained in wide variety of foods and commensal microbiota, we investigated the effects of Dectin-1 signaling on the intestinal immunity. We found that Dectin-1-deficient mice were refractory to dextran sodium sulfate-induced colitis, a model for inflammatory bowel diseases, due to expansion of one genus of Gram-positive commensal bacteria in the colon associated with remodification of T cell subpopulations. Furthermore, oral administration of a seaweed-derived Dectin-1 antagonist, inhibited the proinflammatory cytokine production in colonic lamina propria cells and suppressed the development of colitis. These observations suggest that inhibition of Dectin-1 signaling in the colon regulates the balance of intestinal microbiota and cellular immunity, and further suppresses the development of inflammatory bowel diseases.

Research Products

• [Journal Article] The Antimicrobial Protein REG3A Regulates Keratinocyte Proliferation and Differentiation after Skin Injury (2012)
  • Author(s): Yuping Lai, Dongqing Li, Changwei Li, Beda Muehleisen, Katherine A. Radek, Hyun Jeong Park, Ziwei Jiang, Zhiheng Li, Hu Lei, Yanchun Quan, Tian Zhang, Yelin Wu, Paul Kotol, Shin Morizane, Tissa R. Hata, Keiji Iwatsuki, Ce Tang, and Richard L. Gallo
  • Journal Title: Immunity. Volume: 37(1) Pages: 74-84.
  • Peer Reviewed
• [Journal Article] IL-23 in colitis: targeting the progenitors (2012)
  • Author(s): Ce Tangand Yoichiro Iwakura
  • Journal Title: Immunity. Volume: 37(6) Pages: 957-9.
  • Peer Reviewed
• [Presentation] 炎症性大腸炎の病態形成におけるDectin-1の新規の役割解析 (2013)
  • Author(s): 唐策、神谷知憲、角木基彦、大島健志朗、服部正平、岩倉洋一郎
  • Organizer: 第60回日本実験動物学会総
  • Place of Presentation: つくば国際会議場
  • Year and Date: 20130515-17
• [Presentation] A novel role of dectin-1 signaling in promoting intestinal inflammation (2012)
  • Author(s): Ce Tang, Tomonori Kamina, Motohiko Kadoki, Yoichiro Iwakura.
  • Organizer: 10^<th> Joint Conference of the ISICR and the ICS, Cytokines 2012
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 20120911-14
• [Presentation] IL-17F, rather than Il-17A promotes CD4+T cell activation and Th1-type immunity. (2011)
  • Author(s): Ce Tang, Shigeru Kakuta, Motohiko Kadoki, Yoichiro Iwakura.
  • Organizer: 9thJoint Conference of the ICS and ISICR, Cytokines (ISICR)
  • Place of Presentation: Florence, Italy
  • Year and Date: 20111009-12