Vitamin D3 resolved human and experimental asthma via B lymphocyte–induced maturation protein 1 in T cells and innate lymphoid cells
Janina C. Grund, Susanne Krammer, Zuqin Yang, Hannah Mitländer, Manfred Rauh, Sabine Zirlik, Alexander Kiefer, Theodor Zimmermann, Ralf J. Rieker, Carol I. Geppert, Nikolaos G. Papadopoulos, Susetta Finotto
Abstract
Background Vitamin D 3 (VitD 3 ) is known to have immunomodulatory functions, and VitD 3 deficiency is associated with more severe asthma. Objective We aimed to assess the immunoregulatory effects of VitD 3 food supplementation on asthma manifestation, with particular focus on T cells and type 2 innate lymphoid cells. Methods Preschool children and adult asthmatic cohorts were analyzed in the context of VitD 3 supplementation and serum levels. In a murine model of ovalbumin-induced asthma, effects of diet VitD 3 sufficiency and deficiency on T cells and type 2 innate lymphoid cells immune mechanisms were investigated. Results We found less severe and better-controlled asthma phenotypes along with reduced need for steroid medication in preschool children and asthmatic adults with VitD 3 supplementation. VitD 3 serum levels correlated with B lymphocyte–induced maturation protein 1 (Blimp-1) expression in blood peripheral mononuclear cells. VitD 3 -supplement–fed mice showed decreased asthmatic traits, with a decrease in IgE serum levels, reduced airway mucus, and increased IL-10 production by lung cells. Furthermore, we discovered an upregulation of effector T cells and Blimp-1 + lung tissue-resident memory T cells as well as induction of anti-inflammatory Blimp-1 + lung innate lymphoid cells producing IL-10. Conclusion Supplementing VitD 3 resulted in amelioration of clinical asthma manifestations in human studies as well as in experimental allergic asthma, indicating that VitD 3 shifts proinflammatory immune responses to anti-inflammatory immune responses via upregulating Blimp-1 in lung innate lymphoid cells and tissue-resident memory cells.