PWE-046 TH17 cells dominate the colonic mucosal immune response in primary sclerosing cholangitis associated colitis

Introduction Primary sclerosing cholangitis (PSC) is an idiopathic chronic cholestatic liver disease associated with ulcerative colitis (UC). PSC is thought to be a consequence of a genetically predisposition, dysregulated immune response and unknown factors including the gut microbiome. The colonic mucosal immune response in PSC associated colitis (PSC-UC), however, has been poorly defined. In this study, we analysed the characteristics of colonic mucosal CD4 T cells in patients with PSC-UC. Methods Colon biopsies were collected from patients with PSC-UC (n=13), UC (n=10) and controls (n=20). One patient with PSC-UC and one patient with UC was on biologics. Three patients with PSC and three with UC had colonic inflammation. Lamina propria mononuclear cells were analysed by flow cytometry. Results PSC-UC and UC were characterised by a significantly higher frequency of colonic mucosal CCR6 +CD161+Th17 cells compared to controls (17.5% vs 11.1%; p=0.009% and 21.02% vs 11.1%; p=0.01 respectively). CCR6-CXCR3+CCR5+Th1 cells were significantly lower in PSC-UC compared to controls (15.46% vs 24.50% respectively; p 0.01). CD127-CD25+FoxP3+T regulatory cell frequencies was elevated and CCR6-CCR5-CXCR3- Th2 frequencies were reduced only in UC compared to controls (7.6% vs 4.38%; p=0.007% and 14.84% vs 8.77%; p=0.02 respectively). Significantly increased frequencies of IL17 producing CD4 cells were observed in both PSC-UC and UC compared to controls (7.75% vs 4.7%; p Conclusions Our study demonstrates for the first time that the colonic mucosal immune response in PSC-UC is characterised by significantly higher Th17 cells and lower Th1 cells compared to controls. Patients with PSC-UC have higher IL-17 and IL17/IFNγ dual producing CD4 cells. Our findings highlight the need to explore the role of key players such as the gut microbiome in mucosal T cell homeostasis and Th1/Th17 plasticity in PSC.