Vitamin D inhibits pro-inflammatory T cell function in patients with inflammatory bowel disease.
J Crohns Colitis. 2019 May 4. Epub 2019 May 4. PMID: 31051495
BACKGROUND AND AIMS: Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease (IBD). Since vitamin D (vitD) deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles.
METHODS: T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry. To translate these in vitro findings to the clinic, serum vitD concentrations and clinical outcomes were correlated with T cell phenotype and function in a prospective patient cohort.
RESULTS: Incubation of peripheral and intestinal T cells with 1,25(OH)2-vitD resulted in strongly reduced frequencies of pro-inflammatory CD4+ and CD8+ T cells producing IFNγ, IL-17, IL-22, IL-9 and TNF. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with incompliant vitD intake, season of the year and anemia in Crohn's disease (CD) as well as disease activity in ulcerative colitis (UC). Ex vivo immuno-phenotyping revealed that CD4+and CD8+ T cell subsets were not substantially altered in vitD-deficient vs. -sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CD patients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CD patients resultedin significantly reduced frequencies of CD4+ T cells producing IFNγ, IL-17 and IL-22.
CONCLUSION: VitD exerts profound anti-inflammatory effects on peripheral and intestinal CD4+ and CD8+ T cells of IBD patients in vitro and inhibits TH1 and TH17 cytokine production in CD patients in vivo.