Crystalline silica-induced recruitment and immuno-imbalance of CD4+ tissue resident memory T cells promote silicosis progression

• Published in: Communications biology 2024-08, Vol.7 (1), p.971-14, Article 971
• Main Authors: You, Yichuan, Wu, Xiulin, Yuan, Haoyang, He, Yangyang, Chen, Yinghui, Wang, Sisi, Min, Hui, Chen, Jie, Li, Chao
• Format: Article
• Language: English
• Subjects: 631/250/1619/554/1898; 631/250/249/2510; 631/250/256/2515; 64; 64/60; 96; 96/31; Animals; Biomedical and Life Sciences; CD103 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD69 antigen; Disease Progression; Fibrosis; Immunologic Memory; Immunological memory; Interleukin 7; Life Sciences; Lung - immunology; Lung - pathology; Lung diseases; Lymphocytes T; Male; Memory cells; Memory T Cells - immunology; Mice; Mice, Inbred C57BL; Occupational exposure; Phenotypes; Silica; Silicon Dioxide - toxicity; Silicosis; Silicosis - immunology; Silicosis - pathology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06662-z

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 (T RM ) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The T RM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69 + CD103 + T RM -Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the T RM cells into functionally distinct subsets, mirroring the immuno-balance within CD4 + T RM cells. However, targeting CD103 + T RM -Tregs do not mitigate disease phenotype since the T RM 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 + T RM 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 T RM -Teffs and T RM -Tregs promoted silicosis progression. Neutralizing IL-7 alleviated silicosis by disrupting T RM -Teff maintenance.