Synapse - Oxidized thioredoxin-1 restrains the NLRP1 inflammasome

Oxidized thioredoxin-1 restrains the NLRP1 inflammasome Journal Article

Authors:	Ball, D. P.; Tsamouri, L. P.; Wang, A. E.; Huang, H. C.; Warren, C. D.; Wang, Q.; Edmondson, I. H.; Griswold, A. R.; Rao, S. D.; Johnson, D. C.; Bachovchin, D. A.
Article Title:	Oxidized thioredoxin-1 restrains the NLRP1 inflammasome
Abstract:	The danger signals that activate the NLRP1 inflammasome have not been established. Here, we report that the oxidized, but not the reduced, form of thioredoxin-1 (TRX1) binds to NLRP1. We found that oxidized TRX1 associates with the NACHT-LRR region of NLRP1 in an ATP-dependent process, forming a stable complex that restrains inflammasome activation. Consistent with these findings, patient-derived and ATPase-inactivating mutations in the NACHT-LRR region that cause hyperactive inflammasome formation interfere with TRX1 binding. Overall, this work strongly suggests that reductive stress, the cellular perturbation that will eliminate oxidized TRX1 and abrogate the TRX1-NLRP1 interaction, is a danger signal that activates the NLRP1 inflammasome.
Keywords:	genetics; metabolism; adaptor proteins, signal transducing; signal transducing adaptor protein; thioredoxin; nucleotide binding oligomerization domain like receptor; inflammasome; inflammasomes; humans; human; nlrp1 protein, human; nlr proteins; thioredoxins
Journal Title:	Science Immunology
Volume:	7
Issue:	77
ISSN:	2470-9468
Publisher:	Amer Assoc Advancement Science
Date Published:	2022-11-01
Start Page:	eabm7200
Language:	English
DOI:	10.1126/sciimmunol.abm7200
PUBMED:	36332009
PROVIDER:	scopus
PMCID:	PMC9850498
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141890381&doi=10.1126%2fsciimmunol.abm7200&partnerID=40&md5=b7346e0d585081ee1723b8cb050a5a83
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus