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