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J Crohns Colitis. 2019 Feb 4. doi: 10.1093/ecco-jcc/jjz010. [Epub ahead of print]

CD4+ tissue-resident memory T-cells expand and are a major source of mucosal tumor necrosis factor α in active Crohn's Disease.

Author information

1
Division of Gastroenterology, Department of Medicine, University of Michigan.
2
University of Michigan Crohn's and Colitis Program.
3
Tokyo R&D center, Miyarisan Pharmaceutiacal Co.,Ltd.
4
Department of Surgery, University of Michigan.
5
Department of Cell and Developmental Biology, University of Michigan.
6
These authors made equal contributions.

Abstract

Background and Aims:

Tumor necrosis factor (TNF)α and IL-17A producing T-cells are implicated in Crohn's disease (CD). Tissue-resident memory T (TRM) cells are tissue-restricted T-cells that are regulated by PR zinc finger domain 1 (PRDM1), which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defense but their role in CD is unknown. We thus examined CD4+ TRM cells in CD.

Methods:

Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterize CD4+ TRM cells.

Results:

CD4+ TRM cells are the most abundant memory T-cell population and are the major T-cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD that are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T-cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells.

Conclusion:

CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.

PMID:
30715262
DOI:
10.1093/ecco-jcc/jjz010

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