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.
[1]Fudan Univ, Huadong Hosp, Dept Resp & Crit Care Med, Shanghai, Peoples R China.
[2]Kunming Med Univ, Affiliated Hosp 1, Ctr Resp Med, Kunming, Yunnan, Peoples R China.
[3]Tongji Univ, Shanghai Pulm Hosp, Dept Resp & Crit Care Med, Sch Med,Inst Resp Med, Shanghai, Peoples R China.
[4]Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Med, Hong Kong, Peoples R China.
[5]Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China.
[6]Tongji Univ, Tongji Hosp, Dept Resp & Crit Care Med, Shanghai, Peoples R China.
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