title: Control of Circulating IgE by the Vitamin D Receptor In Vivo Involves B Cell Intrinsic and Extrinsic Mechanisms.
abstract: Vitamin D deficiency is associated with the development of asthma and allergy. The active form of vitamin D [1,25(OH)2D] regulates B cells in vitro and mice without the vitamin D receptor (VDR knockout [KO]) have high serum IgE. Whole-body VDR KO, T cell-specific VDR (T-VDR) KO, B cell-specific VDR (B-VDR) KO, and vitamin D deficient mice were used to determine the targets of vitamin D in the regulation of IgE in vivo. Vitamin D deficient, VDR KO, and B-VDR KO mice developed hyper-IgE, whereas T-VDR KO mice did not. The data show that IL-10 secretion by B cells and CD1d expression on IL-10 secreting B cells was lower in VDR KO mice. Mesenteric lymph node cultures from VDR KO and B-VDR KO mice secreted higher IgE ex vivo than wild-type (WT) cultures, and the addition of IL-10 eliminated the difference in IgE production between VDR KO and WT cultures. The increase in IgE in VDR KO mice was 2-fold greater than in the B-VDR KO mice, suggesting that VDR deficiency in non-B cells contributes to hyper-IgE in vivo. Antibiotic depletion of the microbiota raised serum IgE 4-fold in both WT and VDR KO mice. The VDR directly and indirectly regulates IgE production in B cells. Through the VDR, vitamin D is an environmental factor that helps to maintain low serum IgE responses.
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802.|Molecular Medicine Graduate Program, Pennsylvania State University, University Park, PA 16802; and.
authors.forename: Jamaal
authors.initials: J
authors.lastname: James
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weaver
authors.affiliation: Department of Veterinary and Biomedical Science, Pennsylvania State University, University Park, PA 16802; mxc69@psu.edu.|Center for Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, PA 16802.
authors.forename: Margherita T
authors.initials: MT
authors.lastname: Cantorna
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000032:analysis / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood*; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D018167:Receptors, Calcitriol; D016753:Interleukin-10; D007073:Immunoglobulin E