Th1 and Innate Lymphoid Cells accumulate in Primary Sclerosing Cholangitis-associated Inflammatory Bowel Disease.
Gwela A., Siddhanathi P., Chapman RW., Travis S., Powrie F., Arancibia-Cárcamo CV., Geremia A.
Primary sclerosing cholangitis (PSC) is an idiopathic chronic disorder of the hepatobiliary system associated with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). Colitis in patients with PSC and UC (PSC-UC) exhibits characteristic features and is linked to increased colon cancer risk. Genetic studies have identified immune-related susceptibility genes that only partially overlap with those involved in IBD. These observations suggest that PSC-UC may represent a distinct form of IBD. It remains to be elucidated whether different immune-mechanisms are involved in colitis in these patients. We aimed to evaluate systemic and intestinal T-cell and innate lymphoid cell (ILC) responses, previously associated to IBD, in patients with PSC-UC compared to patients with UC and healthy controls.Blood samples and colorectal biopsies were collected from patients with PSC-UC, patients with UC and healthy controls. T-cell and ILC phenotype was analysed by multicolour flow cytometry.Chemokine receptor (CCR) profiling of circulating T-cells showed decreased CCR6-CXCR3+ Th1 cells in PSC-UC, but increased CCR6-CCR4+ Th2 cells only in UC, while increased CCR6+CCR4+ Th17 cells were found in both patient groups compared to healthy controls. Increased frequencies of IFN-γ secreting T-cells were found in the colon of patients with PSC-UC compared to UC. Interestingly, we observed accumulation of ILC in the colon in PSC-UC.Our study suggests that PSC-UC represent a different immunological disorder from UC, characterised by increased intestinal Th1 and ILC responses. These results provide further evidence that PSC-UC may represent a distinct form of IBD.