Targeted deletion of Interleukin-3 results in asthma exacerbations

Julia Kölle; Theodor Zimmermann; Alexander Kiefer; Ralf J Rieker; Paraskevi Xepapadaki; Sebastian Zundler; Nikolaos G Papadopoulos; Susetta Finotto

doi:10.1016/j.isci.2022.104440

Targeted deletion of Interleukin-3 results in asthma exacerbations

iScience. 2022 May 23;25(6):104440. doi: 10.1016/j.isci.2022.104440. eCollection 2022 Jun 17.

Authors

Julia Kölle¹, Theodor Zimmermann², Alexander Kiefer², Ralf J Rieker³, Paraskevi Xepapadaki⁴, Sebastian Zundler⁵, Nikolaos G Papadopoulos^{4

6}, Susetta Finotto¹

Affiliations

¹ Department of Molecular Pneumology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany.
² Children's Hospital, Department of Allergy and Pneumology, Friedrich-Alexander- University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
³ Institute of Pathology, Friedrich-Alexander- University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany.
⁴ Allergy and Clinical Immunology Unit, National and Kapodistrian University of Athens, 2nd Pediatric Clinic, 11527 Athens, Greece.
⁵ Department of Internal Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
⁶ Centre for Respiratory Medicine and Allergy, Division of Infection, Immunity and Respiratory Medicine, University of Manchester, M13 9PL Manchester, UK.

Abstract

The cytokine interleukin-3 (IL-3) acts on early hematopoietic precursor cells. In humans, T_reg 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.

Keywords: Biological sciences; Immunology; immune response.