2. Academic Validation
  3. Mechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression

Mechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression

  • Nat Commun. 2024 Nov 12;15(1):9770. doi: 10.1038/s41467-024-54174-5.
Yangyang He # 1 2 3,  Fan Yang # 1 2,  Lin Yang 1 2,  Haoyang Yuan 1 2,  Yichuan You 1 2,  Yinghui Chen 1 2,  Xiulin Wu 1 2,  Hui Min 4,  Jie Chen 5 6,  Chao Li 7 8
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, PR China.
  • 2 Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
  • 3 Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
  • 4 Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, PR China.
  • 5 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, PR China. jchen@cmu.edu.cn.
  • 6 Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China. jchen@cmu.edu.cn.
  • 7 Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, PR China. lichao@cmu.edu.cn.
  • 8 Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China. lichao@cmu.edu.cn.
  • # Contributed equally.
PMID: 39532893 DOI: 10.1038/s41467-024-54174-5
Abstract

Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)-18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via Caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2-ILC1 conversion, associated with silicosis progression via the Notch3-IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.

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