An Immunoregulatory Role of Interleukin-3 in Allergic Asthma

Krammer S, Yang Z, Zimmermann T, Xepapadaki P, Geppert CI, Papadopoulos NG, Finotto S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 13

Article Number: 821658

DOI: 10.3389/fimmu.2022.821658

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.

Authors with CRIS profile

Involved external institutions

National and Kapodistrian University of Athens Greece (GR)

How to cite

APA:

Krammer, S., Yang, Z., Zimmermann, T., Xepapadaki, P., Geppert, C.-I., Papadopoulos, N.G., & Finotto, S. (2022). An Immunoregulatory Role of Interleukin-3 in Allergic Asthma. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.821658

MLA:

Krammer, Susanne, et al. "An Immunoregulatory Role of Interleukin-3 in Allergic Asthma." Frontiers in Immunology 13 (2022).

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