Fig. 2.

Immune functions of vitamin D in the pathophysiology of AA. 1,25(OH)₂D₃ induces dendritic cells (DC) into a tolerogenic state and increases the CTLA-4 receptor in T cells. In Th1 lymphocytes, VDR stimulation by 1,25(OH)D inhibits IL-1 RNA translation, IL-2 production, and the JAK-STAT pathway. Cytokine production of fibroblasts, histiocytes, and endothelial cells are reduced by 1,25(OH)₂D₃, with decreased levels of IFN-γ, a crucial cytokine in AA, which induces MHC I and II expression in the hair follicle and initiation of the inflammatory process. 1,25(OH)₂D₃ reduces NK production and Th17 functions, the latter by inhibition of nuclear transcription factors RUNx1, RORγι, and NFAT. In contrast, 1,25(OH)₂D₃ stimulates Treg production and functions. CTLA-4, cytotoxic T-lymphocyte antigen 4; JAK, Janus kinase receptor; STAT, signal transducer and activator of transcription protein; CXCL, C-X-C motif ligand; IFNg, interferon gamma; HRE, hormone response element; MHC, major histocompatibility complex; RUNX1, Runt-related transcription factor 1; NFAT, activated T-cell nuclear factor; RORγι, retinoic-acid-receptor-related orphan nuclear receptor gamma; VDR, vitamin D receptor.