title: 1,25-Dihydroxyvitamin D3 alters the profile of bone marrow-derived dendritic cells of NOD mice.
abstract: 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevents autoimmune diabetes in nonobese diabetic (NOD) mice. A major target for 1,25(OH)(2)D(3) in the immune system is the dendritic cell (DC). Since important DC abnormalities have been described in NOD mice, we investigated the effects of 1,25(OH)(2)D(3) on the yield and phenotype of DCs generated from bone marrow of NOD mice compared to control congenic nonobese diabetes-resistant (NOR) mice. In both mouse strains, exposure of the bone marrow-derived cells to 1,25(OH)(2)D(3) increased the proportion of CD11c(+) DCs after culture. Surface expression of MHC II, CD86, and CD54 on NOR-derived DCs was decreased after 1,25(OH)(2)D(3) treatment, while CD40 remained unchanged. On NOD-derived DCs, 1,25(OH)(2)D(3) only inhibited the expression of MHC II and CD86. 1,25(OH)(2)D(3) inhibited IL-12 and IL-10 secretion after IFNgamma and LPS stimulation. In vitro treatment with 1,25(OH)(2)D(3) alters DC yield from bone marrow cultures and alters the phenotype of the cells in NOD as well as in NOR mice. NOD-derived DCs were more resistant to the 1,25(OH)(2)D(3) effects than were NOR-derived DCs.
authors.affiliation: Laboratorium voor Experimentele Geneeskunde en Endocrinologie (LEGENDO), Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: van Etten
authors.forename: Olivier
authors.initials: O
authors.lastname: Dardenne
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.forename: Lut
authors.initials: L
authors.lastname: Overbergh
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D019013:CD40 Antigens / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D012333:RNA, Messenger / Q000187:drug effects; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D003470:Culture Media; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol