Crystalline silica-induced recruitment and immuno-imbalance of CD4+ tissue resident memory T cells promote silicosis progression
Yichuan You, Xiulin Wu, Haoyang Yuan, Yangyang He, Yinghui Chen, Sisi Wang, Hui Min, Jie Chen, Chao Li
Abstract
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 (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.