Mechanism of action of the IBD susceptibility factor CREM in the DSS-colitis model 2628

Abstract Description Shelby L. Schenck, Audrey C. Brown, Christopher F. Pastore, Md Jashim Uddin, and William A. Petri Jr. Nearly 3.1 million Americans are afflicted with inflammatory bowel disease (IBD), a number that is increasing (+169%; 2001-2006 vs. 2016-2021) despite advent of effective biologics. Recent genome-wide association studies (GWAS) have uncovered risk loci (rs11010067, p = 1 X 10-25; rs34779708, p = 2 x 10-25) that confer IBD susceptibility for the gene cAMP-response element modulator (CREM). Additionally, data has demonstrated that Crem mRNA levels are significantly increased in the gut of patients with ulcerative colitis, suggesting CREM promotes IBD. CREM possesses multiple isoforms, including ICER, which is theorized to function in autoinflammation and autoimmunity by altering T cell function in patients with systemic lupus erythematosus. I find that under the oft-utilized murine model of IBD, DSS-colitis, conditional full-body deletion of Crem confers protection from acute DSS treatment (%original weight, p < 2.2 x 10-16; disease activity index, p = 1.78 x 10-8, Type III ANOVA). Preliminary experimentation in adaptive lymphocyte- and intestinal epithelial cell-specific deletions suggest that this phenomenon is at least partly mediated by the immune system. Work is underway to determine the mechanism that CREM employs to promote colitis. Topic Categories Mucosal and Regional Immunology (MUC)