Figure 2.

Intracrine vs paracrine effects of vitamin D on helper and regulatory T cell function. Schematic showing the metabolism of 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D) via 1α-hydroxylase (1α-OHase) activity in antigen-presenting cells such as dendritic cells and T helper (Th)1 cells. Serum transport of 25D by vitamin D-binding protein (DBP) may suppress cellular availability of 25D. Transcriptional response to 1,25D following binding to the vitamin D receptor (VDR) modulates antigen presentation through target molecules such as CD80 and CD86 to influence the activation of quiescent T helper (Th)0 cells to Th1, Th17 , Tfh and regulatory T cells (Treg). These T cell phenotypes require specific cytokines (shown next to arrows). Production of 1,25D by antigen-presenting cells may result in paracrine effects on adjacent VDR-expressing T cells leading to the down or up-regulation of specific T cell cytokines (shown next to the T cell sub-types). Production of 1,25D by Th1 cells may also result in intracrine effects to suppress inflammatory Th1 immunity.