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

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) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The T cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69CD103 T-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the T cells into functionally distinct subsets, mirroring the immuno-balance within CD4 T cells. However, targeting CD103 T-Tregs do not mitigate disease phenotype since the T subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69CD103 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 cells in mediating CS-induced fibrosis and provide potential therapeutic strategies.