The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation

Jonathan Muri, Sebastian Heer, Mai Matsushita, Lea Pohlmeier, Luigi Tortola, Tobias Fuhrer, Marcus Conrad, Nicola Zamboni, Jan Kisielow and Manfred Kopf ()
Additional contact information
Jonathan Muri: Institute of Molecular Health Sciences, ETH Zurich
Sebastian Heer: Institute of Molecular Health Sciences, ETH Zurich
Mai Matsushita: Institute of Molecular Health Sciences, ETH Zurich
Lea Pohlmeier: Institute of Molecular Health Sciences, ETH Zurich
Luigi Tortola: Institute of Molecular Health Sciences, ETH Zurich
Tobias Fuhrer: Institute of Molecular Systems Biology, ETH Zurich
Marcus Conrad: Institute of Developmental Genetics, Helmholtz Center
Nicola Zamboni: Institute of Molecular Systems Biology, ETH Zurich
Jan Kisielow: Institute of Molecular Health Sciences, ETH Zurich
Manfred Kopf: Institute of Molecular Health Sciences, ETH Zurich

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system during thymocyte and peripheral T-cell proliferation, but repression during T-cell quiescence. Deletion of thioredoxin reductase-1 (Txnrd1) prevents expansion the CD4−CD8− thymocyte population, whereas Txnrd1 deletion in CD4+CD8+ thymocytes does not affect further maturation and peripheral homeostasis of αβT cells. However, Txnrd1 is critical for expansion of the activated T-cell population during viral and parasite infection. Metabolomics show that TrxR1 is essential for the last step of nucleotide biosynthesis by donating reducing equivalents to ribonucleotide reductase. Impaired availability of 2′-deoxyribonucleotides induces the DNA damage response and cell cycle arrest of Txnrd1-deficient T cells. These results uncover a pivotal function of the Trx1 system in metabolic reprogramming of thymic and peripheral T cells and provide a rationale for targeting Txnrd1 in T-cell leukemia.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04274-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04274-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04274-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().