title: VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3.
abstract: 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, 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)2D3 in mast cell development and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs.
authors.affiliation: Bioxell SpA, Via Olgettina, 58, 20132 Milano, Italy. enrico.baroni@bioxell.com
authors.forename: Enrico
authors.initials: E
authors.lastname: Baroni
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffi
authors.forename: Fabio
authors.initials: F
authors.lastname: Benigni
authors.forename: Antonia
authors.initials: A
authors.lastname: Monno
authors.forename: Donatella
authors.initials: D
authors.lastname: Carlucci
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018167:Receptors, Calcitriol / Q000378:metabolism*; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D012867:Skin / Q000166:cytology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D018167:Receptors, Calcitriol; D016185:Receptors, Interleukin-3; C118756:dihydroxy-vitamin D3; D014807:Vitamin D