Abstract
BackgroundAllergic asthma is a chronic airway inflammatory disease associated with airway mucus hyper-production. ILC2 cells, which express the Th2 transcription factor GATA3, have been associated with allergic asthma. The cytokine IL-3 is known to support eosinophil, basophil and mucosal mast cell differentiation and survival; however, its role on T regulatory cells as well as on lung ILC2 and in pediatric asthma needs further investigation.ObjectivesTo investigate the role of IL-3 in preschool children and to explore its therapeutic role in experimental asthma.MethodsIn a cohort of preschool children with and without asthma, we analyzed the secretion of IL-3 in nasopharyngeal fluid (NPF) and IL-3 receptor (R) alpha chain mRNA expression in peripheral blood mononuclear cells (PBMCs). In a murine model of allergic asthma, we analyzed the phenotype of wild-type untreated and rIL-3 intranasally treated asthmatic mice.ResultsIL-3 was found downregulated in the nasopharyngeal fluid of children with partially controlled asthma, as compared to control children. Moreover, IL-3 was found induced in phytohemagglutinin (PHA)-stimulated PBMCs from children with asthma and treated with steroids. Finally, IL-3 in NPF directly correlated with the anti-inflammatory molecule sST2 in steroid-treated asthmatic children. Intranasal rIL-3 delivery in vivo during the challenge phase decreased airway mucus production and inflammatory eosinophils. Moreover, rIL-3 given during the challenge phase, reduced lung ST2intGATA3+ILC2, accompanied by an induction of T regulatory cells in the airways.ConclusionsIL-3 was found associated with steroid-resolved asthma. Moreover, treatment with rIL-3 resulted in amelioration of airway eosinophilia and mucus production, two main pathophysiological conditions associated with asthma in a murine model of allergic asthma. Thus, rIL-3 opens new strategies for immunotherapy of this disease.
Highlights
Allergic asthma (AA) is a chronic inflammatory disease of the airways affecting especially children worldwide
By looking closely at their clinical data (Supplementary Table 2), we found that the child with no IL-3 in the nasopharyngeal fluid (NPF) had worse lung function and higher C-reactive protein (CRP), confirming a possible role of IL-3 in the amelioration of asthma
Because IL-3 is known to be released by activated T cells, we challenged the peripheral blood mononuclear cells (PBMCs) with lectin PHA
Summary
Allergic asthma (AA) is a chronic inflammatory disease of the airways affecting especially children worldwide The immunopathology of this disease has been associated with the damage induced to the airways by repeated respiratory triggers like allergens, viruses and bacterial infections in a distinct genetic background. The exact mechanism by which, upon allergen challenge or infection, T cells are activated and drive the airway inflammation seen in allergic asthma needs to be defined [10,11,12]. This airway inflammation encloses the recruitment of cells of the innate immunity, which clear the antigen or infection and return to a homeostatic T-immunosuppressive status. The cytokine IL-3 is known to support eosinophil, basophil and mucosal mast cell differentiation and survival; its role on T regulatory cells as well as on lung ILC2 and in pediatric asthma needs further investigation
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