Th1 and Innate Lymphoid Cells Accumulate in Primary Sclerosing Cholangitis-associated Inflammatory Bowel Disease

• Published in: Journal of Crohn's and colitis 2017-09, Vol.11 (9), p.1124-1134
• Main Authors: Gwela, Agnes, Siddhanathi, Priya, Chapman, Roger W, Travis, Simon, Powrie, Fiona, Arancibia-Cárcamo, Carolina V, Geremia, Alessandra
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers - metabolism; Biopsy; Case-Control Studies; Cholangitis, Sclerosing - complications; Cholangitis, Sclerosing - diagnosis; Cholangitis, Sclerosing - immunology; Cholangitis, Sclerosing - pathology; Colitis, Ulcerative - complications; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - immunology; Colitis, Ulcerative - pathology; Colon - immunology; Colon - pathology; Female; Flow Cytometry; Humans; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Middle Aged; Original; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx050

Abstract 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.