Stat5 in CD4+ T cells counteracts chronic colitis 2461

Abstract Description Inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis are characterized by a massive and uncontrolled infiltration of T cells to the gut. Secretion of proinflammatory cytokines further increases T cell recruitment and activates other effector cells. Signalling via the Jak/Stat pathway plays an important role in this process. However, although Jak inhibitors are used to treat IBD, the specific role of Stat5 on the T cell compartment in the pathogenesis of IBD is still not solved. Therefore, we generated mice with a specific knockout of Stat5a/b in CD4+ T cells. These mice spontaneously developed colitis and disease activity progressively increased over time. Stat5 deficiency led to the infiltration of neutrophils, macrophages and cytotoxic T cells into the inflamed colon as well as a differently regulated mRNA expression of proinflammatory cytokines in LPMCs and lymph nodes from Stat5 deficient compared to control mice. Our observation that Stat5 deficiency in CD4+ T cells drives intestinal inflammation in mice was in line with decreased STAT5a/b expression in colon biopsies from patients with IBD compared with controls. Moreover, flare-free survival was longer in patients with high STAT5 mRNA levels than with low STAT5 mRNA levels. Collectively, Stat5 expression in CD4+ T cells seems to play a crucial regulatory role in chronic intestinal inflammation and might therefore serve as novel therapeutic approach for IBD in the future Funding Sources IZKF (Interdisciplinary Centre for Clinical Research of the University Erlangen-Nünberg) Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)