Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation

•1,25(OH)2D3 and 25(OH)D3 both decreased the secretion of pro-inflammatory cytokines•Vitamin D metabolites increase IL-10 secretion in Th17 cells•Vitamin D reduced the frequency of Th17 cells expressing pathogenic markers•1,25(OH)2D3 and 25(OH)D3 induced CD25hiFoxp3+ CTLA4+ expression•VDR expression is induced in Th17 cells after treatment with both forms of vitamin D

Vitamin D is a secosteroid hormone that plays an important regulatory role in calcium homeostasis and bone metabolism. Immune cells can both produce and respond to 1,25(OH)2D3. CD4 + T cells from vitamin D receptor (VDR) KO mice produce higher levels of IFN-γ and IL-17 than their wild type counterparts, and play a crucial role in the pathogenesis of autoimmune diseases (AID). We are particularly interested in studying the effect of vitamin D on pathogenic Th17 cells in humans.We investigated the in vitro effect of 1,25(OH)2D3 and 25(OH)D3 on the differentiation and cytokine production of primary CD4 + T cells from normal donors, and cultured in Th17 polarizing conditions. Both forms of vitamin D reduced the expression of pathogenic Th17 markers and their secretion of pro-inflammatory cytokines (IL-17A, IFN-γ). Furthermore, both vitamin D forms induced an expansion of CD25hi cells and upregulated their expression of CTLA-4 and Foxp3 regulatory markers.