TY - JOUR T1 - Oxidized thioredoxin-1 restrains the NLRP1 inflammasome JF - bioRxiv DO - 10.1101/2021.09.20.461118 SP - 2021.09.20.461118 AU - Daniel P. Ball AU - Alvin E. Wang AU - Charles D. Warren AU - Qinghui Wang AU - Andrew R. Griswold AU - Sahana D. Rao AU - Daniel A. Bachovchin Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/20/2021.09.20.461118.abstract N2 - At least six human proteins detect danger-associated signals, assemble into complexes called inflammasomes, and trigger pyroptotic cell death. NLRP1 was the first protein discovered to form an inflammasome, but the danger signals and molecular mechanisms that control its activation have not yet been fully established. Here, we report that the NACHT-LRR region of NLRP1 directly binds to oxidized form of thioredoxin-1 (TRX1). We found that NLRP1 requires the ATPase activity of its NACHT domain to associate with TRX1, and that this interaction represses inflammasome activation. Moreover, we discovered that several patient-derived missense mutations in the NACHT-LRR region of NLRP1 weaken TRX1 binding, leading to inflammasome hyperactivation and autoinflammatory disease. Overall, our results establish that oxidized TRX1 binds to and restrains the NLRP1 inflammasome, thereby revealing a link between the cellular redox environment and innate immunity.Competing Interest StatementThe authors have declared no competing interest. ER -