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containing a tripeptide motif glutamic acid-leucine-arginine and one amino acid between the first two cysteines), essential for both neutrophil influx and activation ( Using mouse models of cigarette smoke (CS) exposure and elastase-induced injury, we previously showed that interleukin (IL-) 1 and the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) are essential to promote inflammation, remodeling, and emphysema, suggesting that inflammasome pathways are involved in the establishment of COPD ( NOD-like receptor family pyrin domain containing (NLRP)6 inflammasome composed of NLRP6, ASC, and Casp-1 has been shown to regulate microbiota homeostasis and antibacterial immunity in the intestine ( Here, we demonstrate for the first time that the NLRP6 inflammasome governs lung inflammation from CS by controlling neutrophilic inflammation