CD4+ tissue-resident memory T-cells expand and are a major source of mucosal tumor necrosis factor α in active Crohn’s Disease.
J Crohns Colitis. 2019 Feb 04;:
Authors: Bishu S, El Zaatari M, Hayashi A, Hou G, Bowers N, Kinnucan J, Manoogian B, Muza-Moons MM, Zhang M, Grasberger H, Bourque C, Zou W, Higgins PDR, Spence JR, Stidham RW, Kamada N, Kao JY
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 [PubMed – as supplied by publisher]