Thioredoxin-1 promotes inflammation by regulating NF-kB and NLRP3 inflammasome responses
The thioredoxin-1 system is a key player in maintaining redox homeostasis. However, whether and how this system regulates inflammatory responses remains unknown. A recent publication by the Kopf group (IMHS) shed light on the underlying mechanism.
Macrophages and dendritic cells (DCs) secrete several inflammatory cytokines to orchestrate immune responses. Upon sensing microbial components via Toll-like receptors (TLR), they activate nuclear factor-kB (NF-kB)-dependent transcription of pro-inflammatory cytokines including IL-6, IL-12, and IL-1b. Investigation by Jonathan Muri et al now revealed that Trx1 provides reducing equivalents enabling nuclear NF-kB DNA binding and thereby inflammatory responses in DCs. Interestingly, however, macrophages but not DCs can exclusively tap the glutathione/glutaredoxin pathway to compensate for the absence of Trx1 and to sustain NF-kB responses. Moreover, independent of this activity, Trx1 was found to be critical for NLRP3 inflammasome activation and IL-1b production in macrophages by detoxifying excessive reactive oxygen species (ROS). Therefore, this study suggests that targeting Trx1 may be exploited to treat inflammatory diseases.
Link to the publication in external page Elife