Dendritic cell modulation by the Vitamin D system

Abstract

1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3] is the hormonally active form of vitamin D. This hormone, well known for its key role in the regulation of bone metabolism, exhibits also a wide range of immunoregulatory and anti-in fl ammatory properties. Cells involved in innate and adaptive immune responses, including macrophages, dendritic cells (DCs), and T and B lymphocytes, express the vitamin D receptor (VDR), can produce 1,25(OH)2D3, and respond to this hormone leading to a modulation of both innate and adaptive immune responses. 1,25(OH)2D3 directly induces expression of genes encoding antimicrobial peptides, in particular cathelicidin antimicrobial peptide (CAMP), components of innate immunity controlling bacterial infection that also act as signaling molecules regulating immune responses. 1,25(OH)2D3, via cathelicidin induction, has been found to represent a key link between toll-like receptor activation and antibacterial response in innate immunity. VDR agonists can also modulate adaptive immune responses via a variety of different mechanisms, in particular targeting DCs, the most potent antigen-presenting cells. DCs can either induce or tolerize T cells, and tolerogenic DCs can promote the development of regulatory T cells (Treg) with suppressive activity. VDR agonists therefore shape DC phenotype and function, enhancing their tolerogenicity in adaptive immune responses. 1,25(OH)2D3 and its analogues not only promote induction of Treg cells but can also enhance their recruitment at in fl ammatory sites. Thus, the capacity of VDR agonists to enhance innate immune responses while favoring DC tolerogenicity could contribute to their bene fi cial effects in chronic in fl ammatory and autoimmune diseases.