Discussion
VitD3 influences immune system in asthma.6-8 Here we found that in healthy, but not in asthmatic preschool children serum 25(OH)VitD3 inversely correlated with CRP, a protein upregulated during ongoing inflammation and infections.27Furthermore, we found that, asthmatic children had higher CRP serum level, indicating induced ongoing inflammation. Finally, asthmatic pre-school children which did not receive VitD3 supplementation in infancy had more episodes of asthma exacerbations associated with high serum CRP levels indicating a limiting effect of VitD3 on infection also in preschool children with asthma.
Next, we wanted to see how Vitamin D3 affects T cells activationin vivo in asthma. Therefore we decided to look at PD1, a marker for downregulation of T cell mediated immune responses and also a marker for T cell exhaustion22. We found that control children with high Vitamin D3 serum levels have less PD1 mRNA in their blood cells than those with low VitD3 levels. This was not seen in asthmatic children, indicating the presence of a PD1 inducing pathway in asthma.
To look for a new molecular therapy for allergic asthma, we treated mice intranasally with VitD3 within 20 minutes after OVA allergen challenge. Here, VitD3 induced CD4+T cells and down-regulated Foxp-3 T regulatory cells and PD1 in the lung.
We further demonstrated that VitD3 induced CD4+ T cells after OVA challenge. CD25, Foxp3 and IL10, all markers for T regulatory cells28,29, were increased by OVA and downregulated by VitD3.
Furthermore, some ILC2 inducing markers like IL-33 were reduced by Vitamin D3 combined with allergen, indicating an homeostatic function in the airways of treated mice30. It would be very interesting to know if Vitamin D3 could show a direct prophylactic effect.
Our data show a protective homeostatic effect of VitD3 in vivoand in vitro . Further, considering its limiting effect on lung ILC2, a cell type persistent in the lung of asthmatics, VitD3 given intranasally represent a new avenue for the treatment of asthma especially in asthmatic children.
Here we further found that, Vit D3 induced the number of CD4+ T cells in RV infected lung cells in the absence of ST2. 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.
In addition we found that VitD3, has a suppressive role on CD4+PD1+ T cells involved in T cell exhaustion in the airways in the absence of ST2. These data support an interactive role of ViD3 and ILC2 in the lung that can be used for the treatment of allergic diseases and rhinovirus exacerbations seen in pediatric asthma.6