Airway tolerance induced T regulatory cells and with 1,25 (OH)VitD3 reduced PD1 in the airways of OVA challenged mice
To further analyze the underlined mechanism of VitD3 in airway tolerance, in the same model (Fig 5a) , VitD3 induced CD4+ T cells and reduced CD4+CD25+Foxp-3+ T regulatory cells in the airways(Fig 5b-d) 16. Moreover, allergen challenge induced of IL-10 production, was kept upregulated by VitD3 treatment after anti-CD3 antibody challenge(Fig 5e). Finally, treatment of Vitamin D3 with allergen, reduced significantly PD1 mRNA in the airways (Fig 5f).
Vit D3 rescued CD4+ T cells after RV infection in vitro in the absence of ST2 in lung cells
Murine IL-C2 in the lung were described in a model of influenza, where they promote a pathologic effect on airway hyperresponsivness as well as a protective role in epithelial repair. To understand the effect of ILC2 in RV infection present during allergen challenge and the protective effect of VitD3 on this axis, we challenged in vitro lung cells from wt and ST2-/- mice with OVA and infected them with RV and challenged them with VitD3 (Fig. 6a) . Here we found that, Vit D3 induced the number of CD4+ T cells in RV infected lung cells in the absence of ST2 (Fig 6b) . These experiments further support a CD4+ T cells inducing role of VitD3 in the airways during allergen challenge only in the absence of IL-33/ST2. Thus, IL33/ST2 axis is involved in T cell death induced by rhinovirus.