Vitamin D(3) resolved human and experimental asthma via B lymphocyte–induced maturation protein 1 in T cells and innate lymphoid cells

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.