The study investigates the role of the Nalp3 inflammasome in the development of silicosis, a progressive pulmonary fibrotic disorder caused by inhalation of crystalline silica. The authors demonstrate that the Nalp3 inflammasome is essential for the activation of caspase-1 and the secretion of proinflammatory cytokines (IL-1β and IL-18) in response to silica. Silica-induced activation of the Nalp3 inflammasome requires potassium efflux and the generation of reactive oxygen species (ROS). In a murine model of silicosis, mice deficient in Nalp3 or its adaptor ASC showed reduced pulmonary inflammation and fibrosis compared to wild-type mice. These findings highlight the critical role of the Nalp3 inflammasome in the initial inflammatory response to silica, suggesting it as a potential therapeutic target for silicosis.The study investigates the role of the Nalp3 inflammasome in the development of silicosis, a progressive pulmonary fibrotic disorder caused by inhalation of crystalline silica. The authors demonstrate that the Nalp3 inflammasome is essential for the activation of caspase-1 and the secretion of proinflammatory cytokines (IL-1β and IL-18) in response to silica. Silica-induced activation of the Nalp3 inflammasome requires potassium efflux and the generation of reactive oxygen species (ROS). In a murine model of silicosis, mice deficient in Nalp3 or its adaptor ASC showed reduced pulmonary inflammation and fibrosis compared to wild-type mice. These findings highlight the critical role of the Nalp3 inflammasome in the initial inflammatory response to silica, suggesting it as a potential therapeutic target for silicosis.