Journal of Leukocyte Biology vol:81 issue:1 pages:250-262
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is a secosteroid hormone that regulates bone metabolism, controls calcium homeostasis, and possesses immunomodulatory properties. We show here that 1,25(OH)(2)D(3) contributes to the regulation of development and function of mast cells, which play a critical role in several inflammatory disorders. 1,25(OH)(2)D(3) promotes apoptosis and inhibits maturation of mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast cell differentiation by 1,25(OH)(2)D(3) is observed at discrete, intermediate stages of mast cell development, identified by expression of c-kit, FcepsilonRI, and IL-3 receptor-alpha chain, and depends on the expression of the vitamin D receptor (VDR). It is important that mast cell progenitors obtained from VDR-ablated mice undergo an accelerated maturation in vitro and give rise to more responsive mast cells than wild-type. Furthermore, histological analysis of mast cell density in peripheral tissues reveals a moderate increase in the number of mast cells in the skin of VDR-deficient mice compared with wild-type animals. These data support the hypothesis of a physiological role of 1,25(OH)(2)D(3) in mast cell development and suggest novel, therapeutic uses of 1,25(OH)(2)D(3) analogs.