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Evidence for Interleukin-17C governing interleukin-17A pathogenicity and promoting asthma endotype switching in bronchiectasis

Year: 2025

Type: article

Abstract: The management of bronchiectasis-asthma overlap (BAO) is an important clinical issue to be addressed. Little is known regarding the endotype of BAO. Here we recruit patients with a primary diagnosis of bronchiectasis and co-existing asthma. The levels of interleukin (IL)-17C are positively correlated with the levels of IL-17A or group 3 innate lymphoid cells (ILC3s) in peripheral blood samples from patients with BAO. An in vivo mouse model of Pseudomonas aeruginosa chronic lower respiratory tract infection followed by ovalbumin-induced asthma shows that IL-17C potentiates IL-17A expression via interacting with IL-17 receptor E in ILC3s. Additionally, ablation of Il17re in mice attenuates ILC3 responses and IL-17A-mediated asthma endotype switching towards neutrophilic asthma driven by P. aeruginosa chronic lower respiratory tract infection. Lastly, impaired epithelial barrier integrity by P. aeruginosa exposure is associated with IL-17C production in vitro. Collectively, our study implicates evidence for IL-17C governing IL-17A pathogenicity and promoting asthma endotype switching in bronchiectasis, implicating IL-17C as a potential therapeutic target for individuals with BAO. Bronchiectasis and asthma can co-exist in the same patient, and the characteristics may be different from bronchiectasis alone. Here the authors characterise the function of ILC3 cells and how IL-17C potentiates IL-17A expression promoting a neutrophil dominated asthma endotype in mouse bronchiectasis-asthma models.

Source: Nature Communications

DOI: 10.1038/s41467-025-67769-3