Attenuated T cell activation and rearrangement of T cell receptor β repertoire in silica nanoparticle-induced pulmonary fibrosis of mice

Silica nanoparticles (SiNPs) cause pulmonary fibrosis through a complex immune response, but the underlying mechanisms by which SiNPs interact with T cells and affect their functions remain unclear. The T cell receptor (TCR) repertoire is closely related to T cell activation and proliferation and mediates innate and adaptive immunity. High-throughput sequencing of the TCR enables comprehensive monitoring of the immune microenvironment. Here, the role of the TCRβ repertoire was explored using a mouse model of SiNP-induced pulmonary fibrosis and a co-culture of RAW264.7 and CD4+ T cells. Our results demonstrated increased TCRβ expression and decreased CD25 and CD69 expression in CD4+ T cells from peripheral blood and lung collected 14 days after the induction of pulmonary fibrosis by SiNPs. Simultaneously, SiNPs significantly decreased CD25 and CD69 expression in CD4+ T cells in vitro via RAW264.7 cell presentation. Mechanistically, pLCK and pZap70 expression, involved in mediating T cell activation, were also decreased in the lung of mice with SiNP-induced pulmonary fibrosis. Furthermore, the profile of the TCRβ repertoire in mice with SiNP-induced pulmonary fibrosis showed that SiNPs markedly altered the usage of V genes, VJ gene combinations, and CDR3 amino acids in lung tissue. Collectively, our data suggested that SiNPs could interfere with T cell activation by macrophage presentation via the LCK/Zap70 pathway and rearrange the TCRβ repertoire for adaptive immunity and the pulmonary microenvironment. •Silica nanoparticles inhibited T cell activation via the LCK/Zap70 pathway in mice.•The inhibitory effect of SiNPs was mediated via macrophage presentation in vitro.•The TCRβ repertoire was rearranged in mice with SiNP-induced pulmonary fibrosis.•The specifically amplified amino acids may identify SiNP-specific TCR clones.