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αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Lamb, Christopher A, Mansfield, John C, Tew, Gaik W, Gibbons, Deena, Long, Anna K, Irving, Peter, Diehl, Lauri, Eastham-Anderson, Jeff, Price, Maria B, O'Boyle, Graeme, Jones, David E J, O'Byrne, Sharon, Hayday, Adrian, Keir, Mary E, Egen, Jackson G and Kirby, John A (2017) αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis. Journal of Crohn's & colitis, 11 (5). pp. 610-620. ISSN 1876-4479

Item Type: Article

Abstract

Background and Aims

The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions.

Methods

αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations.

Results

CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control.

Conclusion

αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology.

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More Information

Depositing User: Graeme O'Boyle

Identifiers

Item ID: 9298
Identification Number: https://doi.org/10.1093/ecco-jcc/jjw189
ISSN: 1876-4479
URI: http://sure.sunderland.ac.uk/id/eprint/9298
Official URL: https://academic.oup.com/ecco-jcc/article/11/5/610...

Users with ORCIDS

ORCID for Graeme O'Boyle: ORCID iD orcid.org/0000-0002-0472-8061

Catalogue record

Date Deposited: 09 May 2018 12:23
Last Modified: 04 Feb 2021 18:43

Contributors

Author: Graeme O'Boyle ORCID iD
Author: Christopher A Lamb
Author: John C Mansfield
Author: Gaik W Tew
Author: Deena Gibbons
Author: Anna K Long
Author: Peter Irving
Author: Lauri Diehl
Author: Jeff Eastham-Anderson
Author: Maria B Price
Author: David E J Jones
Author: Sharon O'Byrne
Author: Adrian Hayday
Author: Mary E Keir
Author: Jackson G Egen
Author: John A Kirby

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences > Biomedical Sciences

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