Interplay of vitamin D with T regulatory cells (FOXP3+Treg) and thymic stromal lymphopoietin (TSLP) in children with atopic diseases

In recent years, vitamin D has been postulated as a risk factor for asthma and evidence suggests a connection between vitamin D deficiency with allergy and asthma. There is also an association between the dysregulated immune response marked by an increase in FOXP3+ and IL-10 T-regulatory (Treg) cells with the inflammatory processes of asthma.1 Severe asthma was associated with lower vitamin D levels in one of the observational study.2 An in vitro study noted an increase in the synthesis of IL-10 from Treg and dendritic cells was seen in the presence of exogenous vitamin D.3 In cultured steroid resistance T cells, vitamin D restored the immunosuppressive ability of dexamethasone.4 Low vitamin D levels, i.e. serum 25-OHD3 less than 30ng/ml as insufficient and less than 20ng/ml as deficient, have been positively correlated with atopic diseases.5 there is negative correlation between asthma exacerbation and vitamin D levels.6 The inverse association between serum vitamin D levels and need for corticosteroid use in patients with asthma has also been observed.7 Decreased expression of FOXP3 (Forkhead boxP3) is associated with increased exacerbation of asthma and steroid sensitivity, and decreased formation, production and differentiation of FOXP3+Treg cells.8‒10 Upregulated expression of FOXP3+Treg cells by vitamin D supplementation reverses steroid resistance.11‒12 In what? Furthermore, increased expression of FOXP3+Treg cells in allergen specific immunotherapy correlated with higher serum vitamin D levels.13 Vitamin D potentiates the efficacy of allergen immunotherapy by increasing the anti-inflammatory cytokines (IL10 and TGF-beta) response in an animal model of OVA challenged and sensitized BALB/C mice.14 The association of TSLP with vitamin D and % FOXP3+Treg cells is yet to be fully explored. It has been observed that when 16 human bronchial epithelial celllines were exposed to 50 and 500nM of vitamin D, inactive 25-OHD3 is converted to active 1,25 D3 and there is increase in TSLP mRNA and protein expression levels.15‒16 In our previous report, we showed that higher concentrations of TSLP and IL-33 correlate negatively with Treg cells in children with asthma.17 Until now, no study has demonstrated an association of vitamin D levels with TSLP and T regulatory cells in children with atopic disease.