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VDR‐dependent regulation of mast cell maturation mediated by 1,25‐dihydroxyvitamin D 3
Author(s) -
Baroni Enrico,
Biffi Mauro,
Benigni Fabio,
Monno Antonia,
Carlucci Donatella,
Carmeliet Geert,
Bouillon Roger,
D’Ambrosio Daniele
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0506322
Subject(s) - calcitriol receptor , mast cell , biology , receptor , progenitor cell , endocrinology , vitamin d and neurology , medicine , bone marrow , microbiology and biotechnology , calcitriol , immunology , stem cell , biochemistry
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, FcεRI, and IL‐3 receptor‐α 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.