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- Title
Crystalline silica-induced recruitment and immuno-imbalance of CD4<sup>+</sup> tissue resident memory T cells promote silicosis progression.
- Authors
You, Yichuan; Wu, Xiulin; Yuan, Haoyang; He, Yangyang; Chen, Yinghui; Wang, Sisi; Min, Hui; Chen, Jie; Li, Chao
- Abstract
Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies. Crystalline silica exposure led to CD4+ tissue-resident memory T-cell accumulation. The imbalance of pulmonary TRM-Teffs and TRM-Tregs promoted silicosis progression. Neutralizing IL-7 alleviated silicosis by disrupting TRM-Teff maintenance.
- Subjects
IMMUNOLOGIC memory; SILICA; SILICOSIS; LYMPHOCYTES; PHENOTYPES
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-024-06662-z