Background: Serum 25(OH)-Vitamin D3 (VitD3) deficiency during infancy has been associated with asthma. The potential therapeutic role of VitD3 given in the airways and its interference with the allergen and Rhinovirus was the objective of this study. Methods: In two cohorts of children with and without asthma, serum levels of the C-reactive protein (CRP) were correlated to Serum VitD3 and in peripheral blood T cell inhibitor marker Programmed cell death protein 1 (PD1) mRNA was analyzed. In a murine model, VitD3 was given intranasally in vivo and in vitro to lung cells with allergen and Rhinovirus. Results: In the cohorts of pre-school age children without (control) asthma, CRP and VitD3 levels inversely correlated. In preschool asthmatic children that did not receive VitD3 supplementation as infant had more episode of asthma exacerbation associated with high CRP serum level. In peripheral blood cells from control but not asthmatic children with higher serum levels of VitD3 had lower PD1 mRNA levels. In murine model, OVA intranasal challenge induced Innate Lymphoid Cells type 2 (ILC2)-associated markers and Eosinophils in BALF and VitD3 inhibited lung inflammation and ILC2 markers. Furthermore, VitD3 given intranasally, induced CD4+T cells and reduced PD1, T regulatory cells in the lung. Similarly, VitD3 had a suppressive role on CD4+PD1+ T cells involved in T cell exhaustion in the airways in the absence of ST2 after Rhinovirus infection. Conclusion: These data support an inhibitory role of VitD3 on T cell exhaustion after allergen and rhinovirus infection that is relevant for pediatric asthma.

A document by Marielena Jakobi. Click on the document to view its contents.

Respiratory infections in general and rhinovirus (RV) infection specifically are the main reason for asthma exacerbation in children. Here we found increased level of Programmed cell death protein 1 ligand (PD-L1) mRNA in total blood cells isolated from pre-school children with virus-induced asthma, with lower FEV1% and with high serum levels of the C-Reactive-Protein (CRP). These data indicate that, in the presence of infection in the airways of preschool children, worse asthma is associated with induced PD-L1 mRNA expression. Further, the activation of regulatory elements that induce IFNβ, a cytokine that is involved in immunity of infections, was found to be associated with better lung function in asthmatic children. Finally, IFN-beta released by peripheral blood Mononuclear cells (PBMC) was found associated with an induced expression of PD-L1mRNA in control but no asthmatic children. These data suggest that improving peripheral blood IFN type I expression in PBMCs in pediatric asthma could improve disease exacerbation because suppressing PDL1 expression in blood cells.