3.1 CS particles stimulated CD4+TRM cell emergence and expansion along with silicosis
progression.
First, we utilized the in vivo labeling method distinguishing
tissue-resident cells commonly used in multi-vascular tissues (Fig 1A)[26]. We observed a remarkable appearance of
CD4+ TRM cells
(CD44+CD45 i.v.–) in the silicotic
lung (Fig 1B), whereas few CD4+ TRMcells were found in naive mice. Unlike the circulating
CD4+ TEM cells
(CD44+CD45 i.v.+),
CD4+TRM cells surged continuously with the progression of
silicosis (Fig 1B and Fig S1B), suggesting a causal relation between
CD4+ TRM cells and silicosis
progression. Furthermore, the elevated expressions of cell retention
marker, CD69, CD103, and CXCR6 further confirmed their lung retention
ability (Fig 1C). With the expansion of CD4+TRM cells, there was an increasing number of
CD69+CD103+ and
CD69+CD103–subsets (Fig 1D), implying their
pathogenic role in silicosis. Comparatively, the phenotype of
circulating CD4+TEM cells was analogic in saline and CS-treated mice,
which differed from TRM cells (Fig 1E). Notably, CD69
and CD103 expressions on splenic CD4+TEM cells were not affected by CS injury in the lung
(Fig 1F), indicating CS led to a tissue-local response. Collectively,
these data demonstrated CS stimulated the emergence and expansion of
pulmonary CD4+ TRM cells that were
tightly related to silicosis progression.