Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation
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Academic Press Inc.
Abstract
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-gamma 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-gamma). Furthermore, both vitamin D forms induced an expansion of CD25hi cells and upregulated their expression of CTLA-4 and Foxp3 regulatory markers.
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Active transport, cell nucleus/drug effects, Cd4-positive t-lymphocytes/cytology/drug effects/metabolism, Ctla-4 antigen/metabolism, Calcifediol/pharmacology, Calcitriol/pharmacology, Cell differentiation/drug effects, Cell nucleus/drug effects/metabolism, Cells, cultured, Flow cytometry, Forkhead transcription factors/metabolism, Gene expression/drug effects, Humans, Interferon-gamma/metabolism, Interleukin-10/metabolism, Interleukin-17/metabolism, Receptors, calcitriol/genetics/metabolism, Reverse transcriptase polymerase chain reaction, T-lymphocytes, regulatory/drug effects/metabolism, Th17 cells/cytology/drug effects/metabolism, Vitamins/pharmacology, Il-17a, Th17, Vitamin d