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Chengxian Xu, Shaogang Sun, Travis S. Johnson, Rong Amy Qi, Siyuan Zhang, Jie Zhang, Kai Yang
T regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that glutathione peroxidase 4 (Gpx4) prevents Treg cells from lipid peroxidation and ferroptosis in regulating immune homeostasis and antitumor immunity. Treg-specific deletion of Gpx4 impairs immune homeostasis without substantially affecting survival of Treg cells at steady state. Loss of Gpx4 results in excessive accumulation of lipid peroxides and ferroptosis of Treg cells upon T cell receptor (TCR)/CD28 co-stimulation. Neutralization of lipid peroxides and blockade of iron availability rescue ferroptosis of Gpx4-deficient Treg cells. Moreover, Gpx4-deficient Treg cells elevate generation of mitochondrial superoxide and production of interleukin-1β (IL-1β) that facilitates T helper 17 (TH17) responses. Furthermore, Treg-specific ablation of Gpx4 represses tumor growth and concomitantly potentiates antitumor immunity. Our studies establish a crucial role for Gpx4 in protecting activated Treg cells from lipid peroxidation and ferroptosis and offer a potential therapeutic strategy to improve cancer treatment.
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Xu, C., Sun, S., Johnson, T. S., Qi, R. A., Zhang, S., Zhang, J., & Yang, K. (2021). The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity. Cell Reports, 35(11), 109235. https://doi.org/10.1016/j.celrep.2021.109235
Xu, Chengxian, et al. "The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity." Cell Reports, vol. 35, no. 11, 2021, pp. 109235, https://doi.org/10.1016/j.celrep.2021.109235.
Xu, Chengxian, Shaogang Sun, Travis S. Johnson, Rong Amy Qi, Siyuan Zhang, Jie Zhang, and Kai Yang. "The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity." Cell Reports 35, no. 11 (2021): 109235. https://doi.org/10.1016/j.celrep.2021.109235.
Xu C., Sun S., Johnson T. S. [и др.] The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity // Cell Reports. — 2021. — Vol. 35, № 11. — P. 109235. — URL: https://doi.org/10.1016/j.celrep.2021.109235
@article{xu2021glutathione,
title = {{The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity}},
author = {Chengxian Xu and Shaogang Sun and Travis S. Johnson and Rong Amy Qi and Siyuan Zhang and Jie Zhang and Kai Yang},
journal = {Cell Reports},
year = {2021},
volume = {35},
number = {11},
pages = {109235},
doi = {10.1016/j.celrep.2021.109235},
url = {https://doi.org/10.1016/j.celrep.2021.109235}
}TY - JOUR AU - Xu, Chengxian AU - Sun, Shaogang AU - Johnson, Travis S. AU - Qi, Rong Amy AU - Zhang, Siyuan AU - Zhang, Jie AU - Yang, Kai TI - The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity JO - Cell Reports VL - 35 IS - 11 SP - 109235 PY - 2021 DA - 2021/06/01 DO - 10.1016/j.celrep.2021.109235 UR - https://doi.org/10.1016/j.celrep.2021.109235 ER -
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