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
  • 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. [email protected].
  • 10. Shandong Provincial Key Medical and Health Discipline, Qilu Hospital of Shandong University, Jinan, China. [email protected].
  • # Contributed equally.
PMID: 39438439 DOI: 10.1038/s41467-024-53307-0
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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