Up-regulated GSDMD-dependent pyroptosis in pulmonary macrophages of silicosis lungs from human and mice. (A) scRNA-seq of healthy and silicosis lung tissue from human lung transplant patients and donors as well as control and silicosis C57BL/6J mouse models. (B) Cell cluster analysis in silicosis patient lung tissue. (C) mRNA expression levels of GSDMD, CASP1, CASP4, and CASP5 in different cell types of silicosis patient lung tissue. (D) Cell clusters in lung tissue of silicosis mice. (E) mRNA expression levels of Gsdmd, Casp1, and Casp11 in different cell types in lung tissue of silicosis mice. (F, G) IF staining of macrophage marker CD68 (green), GSDMD (red), and DAPI (blue) in lung sections from human silicosis patients and silicosis mice. Dashed boxes show magnified field of view. Arrowheads indicate the colocalization of CD68 and GSDMD. Scale bar, 10 μm (short) and 5 μm (long).