IL-1β-induced epithelial cell and fibroblast transdifferentiation promotes neutrophil recruitment in chronic rhinosinusitis with nasal polyps.

Autor: Xie X; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Wang P; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Jin M; Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China., Wang Y; Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China., Qi L; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Wu C; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Guo S; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Li C; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Zhang X; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Yuan Y; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Ma X; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Liu F; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Liu W; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Liu H; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China., Duan C; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Ye P; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Li X; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China., Borish L; Departments of Medicine, University of Virginia Health System, Charlottesville, VA, USA.; Departments of Microbiology, University of Virginia Health System, Charlottesville, VA, USA., Zhao W; Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, China.; Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, China., Feng X; Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China. drfengxin@sdu.edu.cn.; Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China. drfengxin@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 22; Vol. 15 (1), pp. 9101. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1038/s41467-024-53307-0
Abstrakt: Neutrophilic inflammation contributes to multiple chronic inflammatory airway diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), and is associated with an unfavorable prognosis. Here, using single-cell RNA sequencing (scRNA-seq) to profile human nasal mucosa obtained from the inferior turbinates, middle turbinates, and nasal polyps of CRSwNP patients, we identify two IL-1 signaling-induced cell subsets-LY6D + club cells and IDO1 + fibroblasts-that promote neutrophil recruitment by respectively releasing S100A8/A9 and CXCL1/2/3/5/6/8 into inflammatory regions. IL-1β, a pro-inflammatory cytokine involved in IL-1 signaling, induces the transdifferentiation of LY6D + club cells and IDO1 + fibroblasts from primary epithelial cells and fibroblasts, respectively. In an LPS-induced neutrophilic CRSwNP mouse model, blocking IL-1β activity with a receptor antagonist significantly reduces the numbers of LY6D + club cells and IDO1 + fibroblasts and mitigates nasal inflammation. This study implicates the function of two cell subsets in neutrophil recruitment and demonstrates an IL-1-based intervention for mitigating neutrophilic inflammation in CRSwNP.
(© 2024. The Author(s).)
Databáze: MEDLINE
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