Oxidized Thioredoxin-1 Restrains the NLRP1 Inflammasome

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2022 Nov 4

PMID 36332009

Authors

Daniel P Ball

Lydia P Tsamouri

Alvin E Wang

Hsin-Che Huang

Charles D Warren

Qinghui Wang

Isabelle H Edmondson

Andrew R Griswold

Sahana D Rao

Darren C Johnson

Daniel A Bachovchin

Affiliations

Soon will be listed here.

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.

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