Introduction
Allergic asthma is a chronic-inflammatory disease of the airways that affects millions of people worldwide especially children1,2.
Different pathological form of hyperreaction to allergen, like allergic asthma, atopic dermatitis and food allergy are associated to allergy-induced local inflammation driven by Th2 driven immune-reaction3,4. By contrast, under homeostatic conditions, the airways are kept pathogen free by the function of cells of the innate immunity5. Moreover, 1,25-Dihydroxyvitamin D3 (VitD3) has been suggested as a therapeutic compound for allergic asthma.6-8 In Germany, VitD3 is given to the infants as supplement9 to avoid immunological suppression especially in children which could not receive breastfeeding. Wheezing is associated with asthma in the first years of life.10 Moreover, RV is the factor that associated with wheezing in infants. In this study, we wanted to better understand the role of Vitamin D3 in pediatric asthma.
Most of the medication for asthma are given directly into the airways, we thus thought to investigate in murine model, the role of VitD3 given intranasally in vivo . Recent studies described the role Innate lymphoid cells (ILC2s) in the airways in models of allergic asthma.11-13 When the allergen enters the airways, it interacts with epithelial cells, first. This interaction results in epithelial release of alarmins like IL-33, which activate ILC2 via ST214. Once stimulated, ILC2s secrete IL-5, IL-9 and IL-13, classically known as Th2 cytokines.
Here we focused on the influence of VitD3 in blood cells from two pediatric cohorts with and without asthma. Moreover, we analysed the effect of VitD3 given intranasally, on allergen induced airway tolerance with focus on T regulatory cells and Innate Lymphoid Cell associated markers. 15
The role of T regulatory immunosuppressive cells has been extensively studied in airway tolerance16,17, by contrast, the role of ILC2 in airway tolerance is less understood.
Here we found that VitD3 inhibited key ILC2/ST2 markers like IL-33, Amphiregulin (AREG) and Ror-alpha, and PD1 and induced CD4+ T cells,in vivo in the airways. 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.
Our findings suggest a protective role of VitD3 in antagonizing ILC2 markers in preschool children thus providing a rationale for exploring VitD3 in immunotherapy in pediatric asthma.