Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip

• DOI: 10.7554/elife.53627
• Publication Date: 2020-02-25T13:00:26Z
• Authors: Jonathan Muri; Helen Thut; Qian Feng; Manfred Kopf
• Keywords: Thioredoxin-Interacting Protein; Glutaredoxin

Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role T cells, murine Trx1 system dispensable for steady-state myeloid-cell hematopoiesis due their capacity tap glutathione/glutaredoxin pathway DNA biosynthesis. instrumentally enables nuclear NF-κB DNA-binding thereby pro-inflammatory responses monocytes dendritic cells. Moreover, independent this activity, NLRP3 inflammasome activation IL-1β production macrophages by detoxifying excessive ROS levels. Notably, exclude involvement inhibitor Txnip a redox-sensitive ligand previously proposed. Together, study suggests targeting may be exploited treat inflammatory diseases.