Josefine Schardey1, Anna-Maria Globig1,2, Christine Janssen1, Maike Hofmann1, Philipp Manegold3, Robert Thimme1, Peter Hasselblatt1. 1. Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. 2. Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Germany. 3. Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
Abstract
BACKGROUND AND AIMS: Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because 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 interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn's disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-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 resulted in 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.
BACKGROUND AND AIMS: Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because 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 IBDpatients, 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 interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBDpatients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn's disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CDpatients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CDpatients resulted in 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 IBDpatients in vitro and inhibits TH1 and TH17 cytokine production in CDpatients in vivo.
Authors: Christine Elisabeth Janssen; Anna Maria Globig; Andrea Busse Grawitz; Dominik Bettinger; Peter Hasselblatt Journal: PLoS One Date: 2019-05-23 Impact factor: 3.240