The thioredoxin-1 system fuels DNA biosynthesis during lymphocyte metabolic reprogramming
The thioredoxin-1 and the glutathione/glutaredoxin-1 systems are key players in preserving cytosolic redox balance. How these redox systems serve cellular and humoral immunity mediated by T cells and B cells, respectively, remains unknown. Two recent publications by the Kopf group (IMHS) revealed the underlying mechanism.
Lymphocyte activation leads to a switch from oxidative phosphorylation to aerobic glycolysis to satisfy the increased metabolic demands of proliferating cells. Investigations by Jonathan Muri et al now revealed that T cells exploit the thioredoxin-1 (Trx1) pathway to provide reducing power for the synthesis of DNA building blocks by ribonucleotide reductase at the last step of the pentose phosphate pathway. Interestingly, while T cells are absolutely dependent on the Trx1 system for efficient expansion, B cells with a defective thioredoxin system can rearrange their redox system and utilize the glutathione/glutaredoxin-1 pathway as a backup for development and immune responses. These findings may have profound implications for therapies of B and T cell neoplasms.
Link to the publication in external page Nature Communications"
Link to the publication in external page European Journal of Immunology