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

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: クローン病 / NOD2 / TLR / 粘膜免疫

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 Issue: 3 Pages: 914-24
  • DOI: 10.1002/art.33386
  • NAID: 40019474430
  • Peer Reviewed
• [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 Issue: 10 Pages: e561-e567
  • DOI: 10.1111/j.1365-2893.2011.01478.x
  • Peer Reviewed
• [Journal Article] Activation of type I IFN signaling by NOD1 mediates mucosal host defense against Helicobacter pylori infection (2011)
  • Author(s): Watanabe Tomohiro, et al
  • Journal Title: Gut Microbes Volume: 2 Pages: 61-65
  • Peer Reviewed
• [Journal Article] NOD1contributes to mouse host defenseagainst Helicobacter pylori viainduction of type I IFN and activationof the ISGF3 signaling (2010)
  • Author(s): Watanabe T, Asano N, Fichtner-Feigl S,Gorelick PL, Tsuji Y, Matsumoto Y, ChibaT, Fuss IJ, Kitani A, Strober W
  • Journal Title: J Clin Invest Volume: 120 Issue: 5 Pages: 1645-1662
  • DOI: 10.1172/jci39481
  • Peer Reviewed
• [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 Issue: 6 Pages: 853-861
  • 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 Issue: 4 Pages: 542-5
  • DOI: 10.1136/gut.2009.200972
  • NAID: 120002191881
  • Peer Reviewed
• [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 Issue: 2 Pages: 222-31
  • DOI: 10.1111/j.1478-3231.2009.02092.x
• [Journal Article] NOD1 contributes to mouse host defense against Helicobacter pylori viainduction of type I IFN and activation of the ISGF3 signaling pathway (2010)
  • Author(s): Watanabe Tomohiro, et al
  • Journal Title: Journal of Clinical Investigation Volume: 120 Pages: 1645-1662
  • Peer Reviewed
• [Journal Article] NOD1 contributes to mouse host defense against Helicobacter pylori viaindution of type I IFN and activation of the ISGF3 signaling pathway (2010)
  • Author(s): Watanabe Tomohiro, et al.
  • Journal Title: Journal of Clinical Investigation (in press)
  • Peer Reviewed