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

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 D-3 treatment in healthy subjects. Ten healthy subjects received a total of 480,000 IU oral vitamin D-3 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. 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-beta (p = 0.048), TNF-alpha (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-beta, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin. 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.