Induced and spontaneous colitis mouse models reveal complex interactions between IL-10 and IL-12/IL-23 pathways.

Induced and spontaneous colitis mouse models reveal complex interactions between IL-10 and IL-12/IL-23 pathways. Cytokine. 2019 May 31;121:154738 Authors: Hurtubise R, Audiger C, Dominguez-Punaro MC, Chabot-Roy G, Chognard G, Raymond-Marchand L, Coderre L, Chemtob S, Michnick SW, Rioux JD, Lesage S Abstract Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD). These idiopathic and chronic diseases result from inflammation of the gastrointestinal tract and are mainly mediated by the immune system. Genome wide association studies link genes of the IL-12 and IL-23 biology to both CD and UC susceptibility. IL-12 and IL-23 cytokines share a functional subunit, p40, and their respective receptors also share a functional subunit, IL-12Rβ1. However, clinical trials targeting p40, and thus inhibiting both IL-12 and IL-23 pathways, provided mitigated effects on IBD, suggesting context dependent effects for each cytokine. In addition to IL-12 and IL-23, genetic deficiencies in IL-10 also result in severe IBD pathology. We generated various mouse models to determine how IL-12 or IL-23 interacts with IL-10 in IBD pathology. Whereas defects in both IL-10 and IL-12R do not impact the severity of the Dextran Sulfate Sodium (DSS)-induced colitis, combined deficiencies in both IL-10 and IL-23R aggravate the disease. In contrast to DSS-induced colitis, defects in IL-12R and IL-23R both protect fr...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research