CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn's Disease. (4th February 2019)

• Record Type: Journal Article
• Authors: Bishu, Shrinivas; El Zaatari, Mohammed; Hayashi, Atsushi; Hou, Guoqing; Bowers, Nicole; Kinnucan, Jami; Manoogian, Beth; Muza-Moons, Michelle; Zhang, Min; Grasberger, Helmut; Bourque, Charlie; Zou, Weiping; Higgins, Peter D R; Spence, Jason R; Stidham, Ryan W; Kamada, Nobuhiko; Kao, John Y
• Is Part Of: Journal of Crohn's and colitis. Volume 13:Number 7(2019)
• Page Start: 905
• Page End: 915
• Publication Date: 2019-02-04
• Subjects: T cells -- tissue resident memory T cells -- Crohn's disease -- TNF -- Th17 cells; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjz010
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: Tumour 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 Th 17 cell responses. TRM cells provide host defence 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 characterise 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 which 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 Conclusions: CD4 + TRM cells are expanded in CD and are a major source of TNFα, suggesting that 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.