Development of a new therapy for Crohn's disease by using immuno-regulatory function of NOD2

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Tomohiro 京都大学, 医学研究科, 准教授 (40444468)
• Project Period (FY): 2009 – 2011
• Keywords: クローン病 / NOD2 / TLR

Research Abstract

Healthy gut mucosa exhibit tolerogenic responses to intestinal microflora. Excessive immune-reactions against intestinal microflora lead to the development of inflammatory bowel diseases. Mutations in NOD2 are associated with the development of Crohn's disease. Elucidation of mechanisms by which NOD2 mutations cause Crohn's disease provides new insights in the pathogenesis of colitis. Here we show that NOD2 activation inhibits both NF-. B activation and type I IFN production mediated by TLRs.

Research Products

• [Journal Article] Activation of Toll-like receptors and NOD-like receptors is involved in enhanced IgG4 responses in autoimmune pancreatitis. (2012)
  • Author(s): Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa, M, Kodama Y, Uchida K, Okazaki K, Chiba T.
  • Journal Title: Arthritis & Rheumatism Volume: 64 Pages: 914-24
  • DOI: doi:10.1002/art.33386.
• [Journal Article] Correlation between hypo responsiveness to Toll-like receptor ligands and liver dysfunction in patients with chronic hepatitis virus C infection. (2011)
  • Author(s): Chung H, Watanabe T, Kudo M, Chiba T.
  • Journal Title: Journal of Viral Hepatitis Volume: 18 Pages: e561-e567
  • DOI: doi:10.1111/j.1365-2893.2011.01478.x
• [Journal Article] NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. (2010)
  • Author(s): Watanabe T, Asano N, Fichtner-Feigl S, Gorelick PL, Tsuji Y, Matsumoto Y, Chiba T, Fuss IJ, Kitani A, Strober W.
  • Journal Title: Journal of Clinical Investigation Volume: 120 Pages: 1645-62
  • DOI: doi:10.1172/JCI39481.
• [Journal Article] Hepatitis C virus core protein induces homo-and cross-tolerance to Toll-like receptor ligands via activation of Toll-like receptor (2010)
  • Author(s): Chung H, Watanabe T, Kudo M, Chiba T.
  • Journal Title: Journal of Infectious Diseases Volume: 202 Pages: 853-861
  • DOI: doi:10.1086/655812
• [Journal Article] Possible involvement of T helper type 2 responses to Toll-like receptor ligands in IgG4-related sclerosing disease. (2010)
  • Author(s): Akitake R, Watanabe T, Zaima C, Uza N, Ida H, Tada S, Nishida N, Chiba T.
  • Journal Title: Gut Volume: 59 Pages: 542-5
  • DOI: doi:10.1136/gut.2009.200972
• [Journal Article] Identification and characterization of IgG4-associated autoimmune hepatitis. (2010)
  • Author(s): Chung H, Watanabe T, Kudo M, Maenishi O, Wakatsuki Y, Chiba T.
  • Journal Title: Liver International Volume: 30 Pages: 222-31
  • DOI: doi:10.1111/j.1478-3231.2009.02092.x