Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity
Vitamin D has received increased attention recently for its pleiotropic actions on many chronic diseases. The importance of vitamin D on the regulation of cells of the immune system has gained increased appreciation over the past decade with the discovery of the vitamin D receptor (VDR) and key vitamin D metabolizing enzymes expressed by cells of the immune system. Animal studies, early epidemiologic and clinical studies have supported a potential role for vitamin D in maintaining immune system balance. The hormonal form of vitamin D up-regulates anti-microbial peptides, namely cathelicidin, to enhance clearance of bacteria at various barrier sites and in immune cells. Vitamin D modulates the adaptive immune system by direct effects on T cell activation and on the phenotype and function of antigen-presenting cells (APCs), particularly of DCs. The purpose of this manuscript is to review the molecular and clinical evidence for vitamin D as a modulator of the innate and adaptive immune system.
Innate and adaptive immune balance
Potent immunomodulatory activities of vitamin D on both innate and adaptive immune responses have been recently discovered [12, 22, 25, 99, 107–114]. While innate immunity is enhanced against “high-affinity” foreign antigens, vitamin D sufficiency has a dampening effect on the processing of “low-affinity” self antigens. Although the precise mechanisms are still being discovered, the important role of vitamin D in maintaining immune homeostasis should not be overlooked. Interventional studies to further define the immunomodulatory effects of vitamin D in humans need to be done.
In summary, the effects of 1,25(OH)2D on the immune system include decreasing Th1/Th17 CD4+ T cells and cytokines, increasing regulatory T cells, downregulation of T cell-driven IgG production and inhibition of dendritic cell differentiation. While enhancing protective innate immune responses, 1,25(OH)2D helps maintain self-tolerance by dampening overly zealous adaptive immune responses .