Control of Circulating IgE by the Vitamin D Receptor In Vivo Involves B Cell Intrinsic and Extrinsic Mechanisms [IMMUNE REGULATION]

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.

Footnotes

  • This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke Grant NS067563 and National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements Grant AT005378.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    Abx
    antibiotic
    B10
    IL-10 secreting B cell
    BM
    bone marrow
    B-VDR
    B cell–specific VDR
    CNV
    conventional
    Cyp
    Cyp27B1
    D−
    vitamin D deficient
    D+
    vitamin D sufficient
    DC
    dendritic cell
    GF
    germ-free
    iNKT
    invariant NKT
    KO
    knockout
    MLN
    mesenteric lymph node
    PP
    Peyer’s patches
    Treg
    regulatory T cell
    T-VDR
    T cell–specific VDR
    VDR
    vitamin D receptor
    WT
    wild-type.
  • Received July 12, 2016.
  • Accepted November 20, 2016.

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