| First Author | Muri J | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32096759 | Mgi Jnum | J:294330 |
| Mgi Id | MGI:6445272 | Doi | 10.7554/eLife.53627 |
| Citation | Muri J, et al. (2020) Thioredoxin-1 distinctly promotes NF-kappaB target DNA binding and NLRP3 inflammasome activation independently of Txnip. Elife 9:e53627 |
| abstractText | Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how such systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role in T cells, the murine Trx1 system is dispensable for steady-state myeloid-cell hematopoiesis due to their capacity to tap the glutathione/glutaredoxin pathway for DNA biosynthesis. However, the Trx1 pathway instrumentally enables nuclear NF-kappaB DNA-binding and thereby pro-inflammatory responses in monocytes and dendritic cells. Moreover, independent of this activity, Trx1 is critical for NLRP3 inflammasome activation and IL-1beta production in macrophages by detoxifying excessive ROS levels. Notably, we exclude the involvement of the Trx1 inhibitor Txnip as a redox-sensitive ligand of NLRP3 as previously proposed. Together, this study suggests that targeting Trx1 may be exploited to treat inflammatory diseases. |
