Fachbereich Veterinärmedizin



    Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice (2017)

    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Lindner, Juliane
    Rausch, Sebastian (WE 6)
    Treptow, Sandra
    Geldmeyer-Hilt, Kerstin
    Krause, Tina
    St-Arnaud, René
    Arabian, Alice
    Radbruch, Andreas
    Hartmann, Susanne (WE 6)
    Worm, Margitta
    Heine, Guido
    Journal of immunology — S. 1
    ISSN: 0022-1767
    DOI: 10.4049/jimmunol.1602080
    Pubmed: 29109124
    Institut für Immunologie und Molekularbiologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    Tel.+49 30 838 - 518 34 Fax.+49 30 838 451 834

    Abstract / Zusammenfassung

    The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1 Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell-specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.