Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflamm

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Allergy, Asthma & Clinical Immunology Open Access

RESEARCH

Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflammation Fei Huang1, Yang‑hua Ju2, Hong‑bo Wang2 and Ya‑nan Li2,3* 

Abstract  Background:  Vitamin D (VitD) can regulate immune responses and maternal VitD-deficiency can affect immune responses in the offspring. This study aimed at investigating the effects of maternal VitD-deficiency during pregnancy on Treg and Breg responses in offspring mice with house dust mite (HDM)-induced allergic airway inflammation. Methods:  Female BALB/c mice were randomized and fed with normal chow or VitD-deficient diet until their offspring weaned. The offspring mice were fed with normal chow and injected with vehicle or HDM to induce allergic airway inflammation. The levels of serum 25(OH)D, cytokines and infiltrate numbers as well as percentages of Tregs and Bregs in the bronchoalveolar lavage fluid (BALF) were analyzed. The relative levels of VitD receptor (VDR), VitDbinding protein (VDBP), Cytochromes P450 (CYP) 27b1, and CYP24A1 mRNA transcripts in the lungs of different groups of mice were measured. Results:  Maternal VitD-deficiency significantly reduced serum 25(OH)D levels in offspring mice. VitD-deficiency significantly increased the relative levels of VDR, VDBP and CYP27B1 mRNA transcripts, but decreased CYP24A1 expression in the lungs of mice. In comparison with the control mice, significantly elevated levels of pro-inflammatory cytokines, increased numbers of lymphocytes and eosinophils, but decreased levels of anti-inflammatory cytokines were detected in the BALF of VitD-deficient mice. VitD-deficiency significantly increased the frequency of Th1, Th2, Th9, Th17 cells, but decreased regulatory T (Tregs) and B cells (Bregs) in the BALF of mice with allergic airway inflammation. Conclusion:  Maternal VitD-deficiency lowed serum 25(OH)D levels and enhanced HDM-induced allergic airway inflammation in the offspring by impairing Breg and Treg responses. Keyword:  Vitamin D deficiency, Pregnant, Offspring, Regulatory T cells, Regulatory B cells, Asthma Background Asthma is a chronic disease and can affect million people yearly in the world, particularly for children. Pathologically, asthma is characterized by airway epithelial inflammation with different types of inflammatory infiltrates. These inflammatory infiltrates *Correspondence: [email protected] 2 Department of Pediatrics, the First Hospital of Jilin University, Changchun 130021, Jilin, China Full list of author information is available at the end of the article

can secrete cytokines to damage the airway epithelium of the lung, leading to hard breath and hypoxia [1]. However, the molecular pathogenesis of allergic airway inflammation remains unclear. Previous studies have shown that allergen-specific inflammatory Th2, Th17 and Th1 cells are crucial for the pathogenesis of allergic airway inflammation [2] and deficiency in anti-inflammatory regulatory T (Tregs) and B cells (Bregs) also contribute