Trx1/TrxR1 system regulates post-selected DP thymocytes survival by modulating ASK1-JNK/p38 MAPK activities

Immunology and Cell Biology
Rong JinYu Zhang

Abstract

A key process in the development of T lymphocyte in the thymus is T-cell receptor (TCR) selection. It is controlled by complex signaling pathways that contain redox-sensitive molecules. However, the redox status early after TCR selection and how redox regulators promote the survival of post-selected DP thymocytes has not been directly addressed. The present study demonstrated that the transition from pre- to post-selected double-positive (DP) stages was accompanied with an increase of reactive oxygen species (ROS) and a transient surge in the expression of a variety of redox regulators. Among them, the thioredoxin (Trx)1/thioredoxin reductase (TrxR)1 system was found to be critically involved in the regulation of cell survival of DP thymocytes, especially that of post-selected CD69(+) subset, as its inhibition caused a specific reduction of these cells both in vitro and in vivo, most likely owing to increased apoptosis. Suppression of the glutathione-dependent redox system, on the other hand, showed no obvious impact. Biochemically, treatment of DP thymcoytes with TrxR1 inhibitor alone or in conjunction with anti-CD3 resulted in enhanced phosphorylation of redox-sensitive ASK-1, JNK and p38 MAPK, and upregulated expression of B...Continue Reading

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Citations

May 30, 2017·Nature Immunology·Stanley AdoroLaurie H Glimcher
May 30, 2017·Cellular & Molecular Immunology·Janyra A EspinozaAlexis M Kalergis
Dec 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shusong ZhangQing Ge
Jul 17, 2020·The Journal of Clinical Investigation·Ying YangAndreas Lundqvist
Jan 26, 2021·Clinical Science·Rui ZhouJingjing Zhang
Aug 15, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bogdan JovanovicGeorg Stoecklin

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