Abstract
Background: 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.
CD4+ tissue-resident memory T cells
(TRM) accumulate in the lung responded to CS particles,
mediating the pathogenesis of silicosis.
Methods: Based on silicosis murine model by single intratracheal
instillation of CS suspension, we further employ adoptive transfer,
FTY720 treatment, and parabiosis murine model to explore their source.
After defining TRM cell subsets by CD103 and CD69, we
intervene CD103+subset and block IL-7 signaling to
alleviate silicosis.
Results: The CD4+ TRM cells are
derived from peripheral lymphocyte recruitment and in situexpansion. Specifically, TRM-Treg cells depend more on
circulating T cell replenishment. The cell retention markers CD103 and
CD69 can divide the TRM cells into effector and
regulatory subsets. However, targeting CD103+TRM-Treg cells do not mitigate disease phenotype since
the TRM subsets exerted immunosuppressive but not
pro-fibrotic roles. We further dissect that
IL-7 signaling promotes the
progression of silicosis by tuning the maintenance of
TRM-effector T cells.
Conclusion: Our findings highlight the distinct role of
CD4+ TRM cells in mediating CS-induced
fibrosis and provide potential therapeutic strategies for silicosis.
Keywords: crystalline
silica; fibrosis; inflammation; silicosis; tissue-resident memory T
cells