Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation
Author(s)
Type
Journal Article
Abstract
Metabolic regulation is a key feature of inflammasome activation and effector function. Using metabolomic approaches, we show that downregulation of taurine metabolism is crucial for NLRP3 inflammasome activation. Following NLRP3 activation stimuli, taurine rapidly egresses to the extracellular compartment. Taurine efflux is facilitated primarily by the volume-regulated anion channel (VRAC). Loss of intracellular taurine impairs sodium-potassium ATPase pump activity, promoting ionic dysregulation and disrupting ionic fluxes. Inhibiting VRAC, or supplementation of taurine, restores the ionic balance, abrogates IL-1β release and reduces cellular cytotoxicity in macrophages. We further demonstrate that the protective effect of taurine is diminished when sodium-potassium ATPase is inhibited, highlighting the pump’s role in taurine-mediated protection. Finally, taurine metabolism is significantly associated with the development of tuberculosis-associated immune reconstitution inflammatory syndrome, a systemic hyperinflammatory condition known to be mediated by inflammasome activation. Altogether, we identified a critical metabolic pathway that modulates inflammasome activation and drives disease pathogenesis.
Date Issued
2025-10-01
Date Acceptance
2025-08-28
Citation
Cell Reports, 2025, 44 (10)
ISSN
2211-1247
Publisher
Elsevier
Journal / Book Title
Cell Reports
Volume
44
Issue
10
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.celrep.2025.116317
Publication Status
Published
Article Number
116317
Date Publish Online
2025-09-18