Dataset Information

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

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 Th17 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.

SUBMITTER: Bishu S

PROVIDER: S-EPMC6939878 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Bishu Shrinivas S El Zaatari Mohammed M Hayashi Atsushi A Hou Guoqing G Bowers Nicole N Kinnucan Jami J Manoogian Beth B Muza-Moons Michelle M Zhang Min M Grasberger Helmut H Bourque Charlie C Zou Weiping W Higgins Peter D R PDR Spence Jason R JR Stidham Ryan W RW Kamada Nobuhiko N Kao John Y JY

Journal of Crohn's & colitis 20190701 7

<h4>Background and aims</h4>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 Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD.<h4>Methods</h4>Colon samples were prospectively collected at endoscopy or surgery in C ...[more]

PMID: 30715262

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Project description:BackgroundDirect comparisons are lacking between vedolizumab and tumour necrosis factor (TNF)-antagonist therapy in Crohn's disease (CD).AimTo compare safety and effectiveness of vedolizumab and TNF-antagonist therapy in adult CD patients.MethodsRetrospective observational cohort (May 2014-December 2017) propensity score-weighted comparison of vedolizumab vs TNF-antagonist therapy (infliximab, adalimumab, certolizumab) in CD. Propensity scores were weighted for age, prior treatments, disease complications, extent and severity, steroid dependence, and concomitant immunosuppressive drug use. The primary outcome was comparative risk for infections or non-infectious serious adverse events (requiring antibiotics, antivirals, antifungals, hospitalisation, or treatment discontinuation, or resulting in death). Secondary comparative effectiveness outcomes were clinical remission (resolution of CD-related symptoms), steroid-free clinical remission and endoscopic remission (absence of ulcers/erosions).ResultsWe included 1266 patients (n = 659 vedolizumab). Rates of non-infectious serious adverse events (odds ratio [OR] 0.072, 95% confidence interval [CI] 0.012-0.242), but not serious infections (OR 1.183, 95% CI 0.786-1.795), were significantly lower with vedolizumab vs TNF-antagonist therapy. Safety comparisons for non-infectious serious adverse events remained significant after adjusting for differences in duration of exposure. No significant difference was observed between vedolizumab and TNF-antagonist therapy for clinical remission (hazard ratio [HR] 0.932, 95% CI 0.707-1.228), steroid-free clinical remission (HR 1.250, 95% CI 0.677-2.310) or endoscopic remission (HR 0.827, 95% CI 0.595-1.151). TNF-antagonist therapy was associated with higher treatment persistence compared with vedolizumab.ConclusionsThere was a lower risk of non-infectious serious adverse events, but not serious infections, with vedolizumab vs TNF-antagonist therapy, with no significant difference for achieving disease remission.

Dataset Information

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

Background and aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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