Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease

<strong>Background and Aims</strong> 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 f...

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Main Authors: Gwela, A, Siddhanathi, P, Oxford IBD Cohort Investigators, Chapman, R, Travis, S, Powrie, F, Arancibia-Cárcamo, C, Geremia, A
Format: Journal article
Language:English
Published: Oxford University Press 2017
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author Gwela, A
Siddhanathi, P
Oxford IBD Cohort Investigators
Chapman, R
Travis, S
Powrie, F
Arancibia-Cárcamo, C
Geremia, A
author_facet Gwela, A
Siddhanathi, P
Oxford IBD Cohort Investigators
Chapman, R
Travis, S
Powrie, F
Arancibia-Cárcamo, C
Geremia, A
author_sort Gwela, A
collection OXFORD
description <strong>Background and Aims</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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.
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spelling oxford-uuid:42267834-cca6-450c-a175-6a645089f7862022-03-26T14:47:46ZTh1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:42267834-cca6-450c-a175-6a645089f786EnglishSymplectic Elements at OxfordOxford University Press2017Gwela, ASiddhanathi, POxford IBD Cohort InvestigatorsChapman, RTravis, SPowrie, FArancibia-Cárcamo, CGeremia, A<strong>Background and Aims</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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.
spellingShingle Gwela, A
Siddhanathi, P
Oxford IBD Cohort Investigators
Chapman, R
Travis, S
Powrie, F
Arancibia-Cárcamo, C
Geremia, A
Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title_full Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title_fullStr Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title_full_unstemmed Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title_short Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease
title_sort th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis associated inflammatory bowel disease
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