Interaction of interleukin-17A with a Th2 response in a mouse model of allergic airway inflammation

  • Background: A total of 262 million people worldwide suffer from asthma and 461000 people died from it in 2019. Asthma is a disease with different endotypes defined by the granulocytes found in the asthmatic lung. In allergic asthma, the eosinophilic endotype is present, driven by a TH2 response. A TH17 immune response leads to the neutrophil endotype. This often causes uncontrolled asthma and is triggered by pollutants, microbes, and oxidative stress. It has been described that a significant number of patients with eosinophilic asthma develop mixed granulocytic asthma over time. The severity of asthma in the mixed endotype is related to the proportion of neutrophils in the lungs. Purpose: In this report, we address the question of how a TH2 response interacts with IL-17A in allergic asthma. Methods: To this end, we used a mouse model to induce allergic asthma followed by an aerosol challenge with ovalbumin. To investigate the role of IL-17A, we administered IL-17A intranasally during the challenge phase. Results: IL-17A alone did not elicit an immune response, whereas in combination with allergic asthma, it resulted in a shift of the asthmatic endotype from eosinophilic to neutrophilic. TGF\(\beta\)1 was increased in these lungs compared to asthmatic lungs without IL-17A, as was the expression of the IL-17A receptor subunits IL-17RA and IL-17RC. In cultures with human cells, we also found that IL-17A increased the expression of its receptors only in combination with IL-13. We also found this effect for IL-8, which attracts neutrophils in humans. Conclusions: The TH2 response increased the sensitivity to IL-17A in a mouse asthma model as well as in human cell lines.

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Author:Karin PetersGND, Stefanie ErnstGND, Marcus PetersORCiDGND
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Date of Publication (online):2024/02/08
Date of first Publication:2023/07/04
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Interleukin-13; Interleukin-17; asthma; endotypes; mouse model
Issue:13, Article 1774
First Page:1774-1
Last Page:1774-16
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Abteilung für Experimentelle Pneumologie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International