Vitamin D3 reverses immune tolerance and enhances the cytotoxicity of effector T cells in coal pneumoconiosis

Coal worker's pneumoconiosis (CWP) is a common occupational disease that coal miners are highly susceptible due to long-term exposure to coal dust particles (CDP). CWP can induce the accumulation of immune cells surrounding the bronchioles and alveoli in the lungs, resulting in pulmonary fibrosis and compromised immune function. Using single-cell RNA sequencing (scRNA-Seq), our previous studies disclose that CDP exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis, while Vitamin D3 (VitD3) supplementation reduces CDP-induced cytotoxicity; however, the mechanism by which how VitD3 regulates immune status in coal pneumoconiosis remains unclear. In this study, we elucidated the heterogeneity of pulmonary lymphocytes in mice exposed to CDP and demonstrated the therapeutic efficacy of VitD3 using scRNA-Seq dataset. The validation of key lymphocyte markers and their functional molecules was performed using immunofluorescence. The results demonstrated that VitD3 increased the number of naive T cells by modulating CD4 + T cell differentiation and decreased the number of Treg cells in CDP-exposed mice, thereby enhancing the cytotoxic activity of CD8 + effector T cells. These effects markedly alleviated lung fibrosis and symptoms. Taken together, the mechanism by which VitD3 regulates the functions of lymphocytes in CWP provides a new perspective for further research on the prevention and treatment of CWP. [Display omitted] •We characterized 57,979 T lymphocyte using unbiased single-cell RNA sequencing.•The T lymphocytes of coal pneumoconiosis showed significant heterogeneity.•Vitamin D enhances lung tissue immune tolerance by reducing CMP Treg.•This reveals the T lymphocyte and molecular status of CMP and provides new ideas for the treatment of vitamin D.