Jamontt, Joanna, Clark, Natalie, Petit, Stephanie, Parkinson, Scott James and Smith, Philip (2013) NOD2 signalling promotes hyper-responsive macrophages and colitis in IL-10 deficient mice. Journal of Immunology, 190. ISSN 0022-1767

Abstract

IL-10 contributes to the maintenance of intestinal homeostasis via the regulation of inflammatory responses to enteric bacteria. The clinical relevance of IL-10 has recently been highlighted in IBD patients where loss of IL-10 signalling can result in early onset inflammatory bowel disease (IBD). NOD2 mutations are associated with Crohn’s disease (one of the major forms of IBD), though the precise role of NOD2 in the development of intestinal inflammation remains undefined. To determine the role of NOD2 in the development of colitis on the clinically relevant genetic background of IL-10 deficient signalling we generated mice deficient in IL-10 and NOD2 (IL-10-/- NOD2-/-). Loss of NOD2 in IL-10-/- mice resulted in significant amelioration of chronic colitis indicating that NOD2 signalling promotes the development of intestinal inflammation in IL-10-/- mice. Contrary to previous reports investigating immune function in NOD2-/- mice, T cell proliferative capacity and IL-2 production was not impaired and immune polarization towards type 1 immunity was not affected. However, loss of NOD2 in IL-10 deficient macrophages reduced IL-6, TNF

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/?term...
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/?term...
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/8669