목적: Proper maintenance of mitochondrial homeostasis is important in various inflammatory diseases. However, how regulation of mitochondrial homeostasis can be controlled to regulate inflammasome activation remains largely unknown. 방법:We demonstrate that Sestrin2 (Sesn2) suppresses prolonged NLRP3 inflammasome activation by clearance of mitochondria damaged by immune stimuli. We also demonstrate that bone marrow-derived macrophages (BMDMs) from Sesn2 deficient mice (Sesn2-/-) displayed increases of damaged mitochondria population upon stimulation with LPS and ATP, which resulted in increased mitochondrial ROS. 결과:Increased mitochondrial ROS observed in Sesn2-/- BMDMs induce hyperactivation of NLRP3 inflammasomes, which results in increases of caspase1 activation and inflammatory cytokines such as IL-1β and IL-18. Thus, Sesn2-/- mice higher mortality than Sesn2+/+ mice in two different sepsis models. 결론:Our findings define a unique regulatory mechanism for immunological homeostasis that protects the host from sepsis.