Targeted deletion of Interleukin-3 results in asthma exacerbations

• DOI: 10.1016/j.isci.2022.104440
• Publication Date: 2022-05-24T01:23:53Z
• Authors: Julia Kölle; Theodor Zimmermann; Alexander Kiefer; Ralf J. Rieker; Paraskevi Xepapadaki; Sebastian Zundler; Nikolaos G. Papad...; Susetta Finotto
• Keywords: 0301 basic medicine; Biological sciences; 03 medical and health sciences; Science; Immunology; Q; immune response; Article; 3. Good health

The cytokine interleukin-3 (IL-3) acts on early hematopoietic precursor cells. In humans, Treg cells secrete IL-3 and repress inflammatory cells except for basophils. The present study aims to elucidate the contribution of IL-3 in the development and the course of allergic asthma. We therefore analyzed the secretion of IL-3 in PBMCs and total blood cells in two cohorts of pre-school children with and without asthma. In a murine model of allergic asthma, we analyzed the phenotype of IL-3-/- mice compared to wild-type mice. PBMCs from asthmatic children showed increased IL-3 secretion, which directly correlated with improved lung function. IL-3-/- asthmatic mice showed increased asthmatic traits. Moreover, IL-3-deficient mice had a defect in T regulatory cells in the lung. In conclusion, IL-3 downregulation was found associated with more severe allergic asthma in pre-school children. Consistently, targeting IL-3 resulted in an induced pathophysiological response in a murine model of allergic asthma.