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Published online before print October 11, 2006

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(Journal of Leukocyte Biology. 2007;81:250-262.)
© 2007 by Society for Leukocyte Biology

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

Enrico Baroni^*,1, Mauro Biffi^*, Fabio Benigni^*, Antonia Monno^*, Donatella Carlucci^*, Geert Carmeliet, Roger Bouillon and Daniele D’Ambrosio^*

^* Bioxell SpA, Milano, Italy; and
Laboratory of Experimental Medicine and Endocrinology, K. Universiteit of Leuven, Leuven, Belgium

¹Correspondence: BioXell S.P.A., Via Olgettina, 58, 20132 Milano, Italy. E-mail: enrico.baroni{at}bioxell.com

1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃] is a secosteroid hormone that regulates bone metabolism, controls calcium homeostasis, and possesses immunomodulatory properties. We show here that 1,25(OH)₂D₃ contributes to the regulation of development and function of mast cells, which play a critical role in several inflammatory disorders. 1,25(OH)₂D₃ promotes apoptosis and inhibits maturation of mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast cell differentiation by 1,25(OH)₂D₃ is observed at discrete, intermediate stages of mast cell development, identified by expression of c-kit, FcRI, and IL-3 receptor- 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)₂D₃ in mast cell development and suggest novel, therapeutic uses of 1,25(OH)₂D₃ analogs.

Key Words: apoptosis • maturation • bone marrow • cell surface molecules

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