An Immunoregulatory Role of Interleukin-3 in Allergic Asthma

Susanne Krammer; Zuqin Yang; Theodor Zimmermann; Paraskevi Xepapadaki; Carol I Geppert; Nikolaos G Papadopoulos; Susetta Finotto

doi:10.3389/fimmu.2022.821658

An Immunoregulatory Role of Interleukin-3 in Allergic Asthma

Front Immunol. 2022 Feb 23:13:821658. doi: 10.3389/fimmu.2022.821658. eCollection 2022.

Authors

Susanne Krammer¹, Zuqin Yang¹, Theodor Zimmermann², Paraskevi Xepapadaki³, Carol I Geppert⁴, Nikolaos G Papadopoulos^{3

5}, Susetta Finotto¹

Affiliations

¹ Department of Molecular Pneumology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
² Children's Hospital, Department of Allergy and Pneumology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
³ Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
⁴ Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
⁵ Centre for Respiratory Medicine & Allergy, Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom.

Abstract

Background: Allergic 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.

Objectives: To investigate the role of IL-3 in preschool children and to explore its therapeutic role in experimental asthma.

Methods: In 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.

Results: IL-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 ST2^intGATA3+ILC2, accompanied by an induction of T regulatory cells in the airways.

Conclusions: IL-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.

Keywords: IL-3; ILC2s; T regulatory cells; allergic asthma; eosinophils.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma* / metabolism
Disease Models, Animal
Humans
Immunity, Innate
Interleukin-3* / metabolism
Leukocytes, Mononuclear / metabolism
Lymphocytes / metabolism
Mice
Mice, Knockout

Substances

IL3 protein, human
Interleukin-3