Figure 2.

Schematic representation of the primary mechanisms through which vitamin D-regulated dendritic cells (DCs) and T-lymphocyte function.

Notes: vitamin D precursors can be further processed to their active metabolite, 1,25(OH)₂D₃, in DCs and T lymphocytes. In DCs, 1,25(OH)₂D₃ binds to the vitamin D receptor–retinoid X receptor (VDR/RXR) complex in the nucleus, leading to a tolerogenic DC phenotype, characterized by decreased expression of major histocompatibility complex (MHC)-II, CD40, CD80, CD86, enhanced expression of immunoglobulin-like transcript (ILT)-3, and increased secretion of interleukin (IL)-10 and CCL22, which results in the induction of T-regulatory (T_reg) cells. The 1,25(OH)₂D₃ signaling in T-cells is dependent on the stimulation of T-cell antigen-receptor (TCR) signaling. VDR expression can be induced by TCR signaling via the alternative p38 MAPK pathway. 1,25(OH)₂D₃ binds to VDR, leading to inhibition of proinflammatory cytokine expression, including interferon (IFN)-γ, IL-17, and IL-21, and promotion of the development of T_reg cells.

Abbreviations: CCL22, chemokine (C-C motif) ligand 22; MAPK, mitogen-activated protein kinase.