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Crystalline silica-induced recruitment and immuno-imbalance of CD4 + tissue resident memory T cells promote silicosis progression.
- Source :
-
Communications biology [Commun Biol] 2024 Aug 09; Vol. 7 (1), pp. 971. Date of Electronic Publication: 2024 Aug 09. - Publication Year :
- 2024
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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 <superscript>+</superscript> tissue-resident memory T cells (T <subscript>RM</subscript> ) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The T <subscript>RM</subscript> cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69 <superscript>+</superscript> CD103 <superscript>+</superscript> T <subscript>RM</subscript> -Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the T <subscript>RM</subscript> cells into functionally distinct subsets, mirroring the immuno-balance within CD4 <superscript>+</superscript> T <subscript>RM</subscript> cells. However, targeting CD103 <superscript>+</superscript> T <subscript>RM</subscript> -Tregs do not mitigate disease phenotype since the T <subscript>RM</subscript> subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69 <superscript>+</superscript> CD103 <superscript>-</superscript> 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 <superscript>+</superscript> T <subscript>RM</subscript> cells in mediating CS-induced fibrosis and provide potential therapeutic strategies.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 39122899
- Full Text :
- https://doi.org/10.1038/s42003-024-06662-z