Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation Through NEK7 Deglutathionylation

The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage associated molecular patterns, triggering production of the proinflammatory cytokines IL-1β and IL-18, promoting pyroptosis. Here, we characterise Glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a novel NLRP3 inflammasome regulator. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown and GSTO1-1-/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. GSTO1-1 is therefore identified as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation.