Figure 5. Regulation of T cells through a paracrine mechanism of vitamin D signaling.

1) 1α-hydroxylase (1α-OHase) gene expression is induced in monocytes by recognition of pathogen associated molecular patterns (PAMP) by toll-like receptors (TLR) and interferon-γ (IFN-γ) from Th1 cells, and in B cells by antigen recognition by the B cell receptor (IgM) along with co-stimulation by antigen-specific T cells. 2) 25-hydroxyvitamin D₃ (25D₃) is converted to 1,25-dihydroxyvitamin D₃ (1,25D₃) by 1α-OHase. 3) 1,25(OH)₂D₃ produced in monocytes and B cells activates the vitamin D receptor (VDR) and enhances iNOS and RANTES expression in monocytes and B cells. 4) 1,25(OH)₂D₃ secreted from monocytes and B cells suppresses IFN-γ and interleukin-17F (IL-17F) expression in T cells. Direct suppression of IFN-γ and IL-17F expression by the 1,25(OH)₂D₃, however, is not certain. Instead, 1,25(OH)₂D₃ may influence T cell development, suppress proliferation, or sensitize them to apoptosis.