VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3

is a secosteroid hormone that regulates bone metab-olism, controls calcium homeostasis, and possesses immunomodulatory properties. We show here that 1,25(OH)2D3 contributes to the regulation of devel-opment and function of mast cells, which play a crit-ical role in several inflammatory disorders. 1,25(OH)2D3 promotes apoptosis and inhibits matu-ration of mouse bone marrow-derived mast cell pre-cursors. Dose-dependent inhibition of mast cell dif-ferentiation by 1,25(OH)2D3 is observed at discrete, intermediate stages of mast cell development, identi-fied by expression of c-kit, FcRI, and IL-3 recep-tor- chain, and depends on the expression of the vitamin D receptor (VDR). It is important that mast cell progenitors obtained fromVDR-ablatedmice un-dergo an acceleratedmaturation in vitro and give rise to more responsive mast cells than wild-type. Fur-thermore, 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)2D3 in mast cell development and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs. J