Vitamin D deficiency in pregnant women impairs regulatory T cell function

Regulatory T cells and IgE receptors (CD23 and CD21) on B cells were assessed in vitamin D deficient pregnant women. For this, 153 pregnant women were recruited from a government hospital and were categorized into three groups based on 25-hydroxyvitamin D3 (25(OH)D3) status. Regulatory T cell population (Treg cells) and CD23/CD21 expression on B cells were quantified by FACS ARIA II in maternal blood at third trimester; and the same parameters were evaluated in cord blood soon after delivery. In addition, TGF β and IL-10 were quantified in maternal and cord blood by using Milliplex kits. In a representative sample of eight women from each group (vitamin D sufficient, insufficient and deficient), placental tissues were processed for mRNA expressions of vitamin D receptor (VDR), retinoic acid receptor (RXR), vitamin D binding protein (VDBP) and vitamin D regulating enzymes. Of the 153 pregnant women, 18 were sufficient (≥30 ng/mL), 55 were insufficient (20-29 ng/mL) and 80 were deficient (≤19 ng/mL) for 25(OH)D3 status. The maternal blood Treg cell population (mean (%)± SE) was lower (p<0.05) in 25(OH)D3 deficient (0.2 ± 0.01) pregnant women compared to insufficient (0.34 ± 0.01) and sufficient (0.45 ± 0.02) pregnant women. Similarly, cord blood Treg cell population (mean (%)± SE) was also lower (p<0.05) in 25(OH)D3 deficient (0.63 ± 0.03) pregnant women when compared to insufficient (1.05 ± 0.04) and sufficient (1.75 ± 0.02) pregnant women. Mean (%) ± SE of B cells with CD23 and CD21 in maternal blood was higher (p<0.05) in 25(OH)D3 deficient pregnant women (0.35 ± 0.02; 1.65 ± 0.04) when compared to insufficient (0.22 ± 0.02; 0.55 ± 0.05) and sufficient (0.15 ± 0.02; 0.21 ± 0.01) pregnant women. Similarly, mean (%)± SE of B cell population with CD23 and CD21 in cord blood was also higher (p<0.05) in 25(OH)D3 deficient (0.41 ± 0.02; 1.2 ± 0.03) when compared to insufficient (0.32 ± 0.01; 0.6 ± 0.05) and sufficient (0.2 ± 0.01; 0.4 ± 0.02) pregnant women. Regulatory cytokines, TGF β and IL-10 were lower (p<0.05) in 25(OH)D3 insufficient and deficient subjects. In the placenta tissue of women with 25(OH)D3 deficiency, the regulatory T cell transcription factor FOXP3, vitamin D receptor (VDR) and retinoic acid receptor (RXR) expressions were downregulated. In contrast, CD23, CD21 and VDBP expressions were upregulated in 25(OH)D3 deficient and insufficient women. Vitamin D regulating enzymes (CYP24A1, CYP2R1 and CYP27B1) expression were also altered in women with 25(OH)D3 deficiency. The current study shows that impaired maternal 25(OH)D3 during pregnancy influences the spectrum of immune cells such as regulatory T cells and B cells with IgE receptors and this in turn may be linked to allergy and asthma in neonates.