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.
Background and Aims: 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 with IBD, in patients with PSC-UC compared with patients with UC and healthy controls. Methods: Blood samples and colorectal biopsies were collected from patients with PSC-UC, patients with UC, and healthy controls. T cell and ILC phenotypes were analysed by multicolour flow cytometry. Results: 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, whereas increased CCR6+CCR4+ Th17 cells were found in both patient groups compared with healthy controls. Increased frequencies of IFN-γ secreting T cells were found in the colon of patients with PSC-UC compared with UC. Interestingly, we observed accumulation of ILC in the colon in PSC-UC. Conclusions: Our study suggests that PSC-UC represents 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.