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

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

  • Nat Commun. 2024 Oct 22;15(1):9101. doi: 10.1038/s41467-024-53307-0.
Xinyu Xie # 1 2 Pin Wang # 1 2 Min Jin # 3 Yue Wang # 4 Lijie Qi 1 2 Changhua Wu 1 Shu Guo 1 Changqing Li 1 Xiaojun Zhang 1 2 Ye Yuan 1 Xinyi Ma 1 Fangying Liu 1 Weiyuan Liu 1 Heng Liu 1 Chen Duan 1 2 Ping Ye 1 2 Xuezhong Li 1 2 Larry Borish 5 6 Wei Zhao 7 8 Xin Feng 9 10
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China.
  • 3 Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.
  • 4 Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China.
  • 5 Departments of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
  • 6 Departments of Microbiology, University of Virginia Health System, Charlottesville, VA, USA.
  • 7 Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, China.
  • 8 Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, China.
  • 9 Department of Otorhinolaryngology, National Health Commission Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, Jinan, China. drfengxin@sdu.edu.cn.
  • 10 Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China. drfengxin@sdu.edu.cn.
  • # Contributed equally.
Abstract

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.

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