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
Affiliations
Julia Kölle
Department of Molecular Pneumology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany
Theodor Zimmermann
Children’s Hospital, Department of Allergy and Pneumology, Friedrich-Alexander- University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
Alexander Kiefer
Children’s Hospital, Department of Allergy and Pneumology, Friedrich-Alexander- University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
Ralf J. Rieker
Institute of Pathology, Friedrich-Alexander- University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany
Paraskevi Xepapadaki
Allergy and Clinical Immunology Unit, National and Kapodistrian University of Athens, 2nd Pediatric Clinic, 11527 Athens, Greece
Sebastian Zundler
Department of Internal Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
Nikolaos G. Papadopoulos
Allergy and Clinical Immunology Unit, National and Kapodistrian University of Athens, 2nd Pediatric Clinic, 11527 Athens, Greece; Centre for Respiratory Medicine and Allergy, Division of Infection, Immunity and Respiratory Medicine, University of Manchester, M13 9PL Manchester, UK
Susetta Finotto
Department of Molecular Pneumology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany; Corresponding author
Summary: 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.
