High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects.

PURPOSE: Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103+DCs of high-dose vitamin D3 treatment in healthy subjects. METHODS: Ten healthy subjects received a total of 480,000 IU oral vitamin D3 over 15 days and colonic biopsies were obtained before and after intervention by endoscopy. Lamina propria mononuclear cells (LPMCs) were isolated from the biopsies, stained with DC surface markers and analysed with flow cytometry. Snap-frozen biopsies were analysed with qPCR for DC and regulatory T cell-related genes. RESULTS: No hypercalcemia or other adverse events occurred in the test subjects. Vitamin D decreased the number of CD103+ DCs among LPMCs (p = 0.006). Furthermore, vitamin D induced mRNA expression of TGF-ß (p = 0.048), TNF-α (p = 0.006) and PD-L1 (p = 0.02) and tended to induce IL-10 expression (p = 0.06). Multivariate factor analysis discriminated between pre- and post-vitamin D supplementation with a combined increased qPCR expression of PD1, PD-L1, TGF-ß, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin. CONCLUSION: High-dose vitamin D supplementation is well tolerated by healthy subjects and has a direct effect on the CD103+ DCs, local cytokine and surface marker mRNA expression in the colonic mucosa, suggestive of a shift towards a more tolerogenic milieu.

Vitamin D increases programmed death receptor-1 expression in Crohn's disease.

BACKGROUND: Vitamin D modulates inflammation in Crohn's disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD. AIM: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo. METHODS: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA. RESULTS: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 - 39%) to 29% (11 - 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 - 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment. CONCLUSIONS: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients.