Details

Autor(en) / Beteiligte

• Yao, Yin
• Chen, Zhian
• Zhang, Hao
• Chen, Cailing
• Zeng, Ming
• Yunis, Joseph
• Wei, Yunbo
• Wan, Yanmin
• Wang, Naiqi
• Zhou, Mingzhe
• Qiu, Chao
• Zeng, Qunxiong
• Ong, Hong Sheng
• Wang, Hao
• Makota, Fadzai Victor
• Yang, Yang
• Yang, Zhaohui
• Wang, Nan
• Deng, Jun
• Shen, Chao
• Xia, Yan
• Yuan, Lin
• Lian, Zhaoqin
• Deng, Yike
• Guo, Cuilian
• Huang, Ao
• Zhou, Pengcheng
• Shi, Haibo
• Zhang, Weitian
• Yi, Hongliang
• Li, Dongmei
• Xia, Ming
• Fu, Jing
• Wu, Ning
• de Haan, Judy B
• Shen, Nan
• Zhang, Wenhong
• Liu, Zheng
• Yu, Di

Titel

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis

Ist Teil von

• Nature immunology, 2021-09, Vol.22 (9), p.1127-1139

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Follicular helper T (T ) cells are a specialized subset of CD4 T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of T cell survival remains unclear. Here we report that T cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for T cell survival. The deletion of GPX4 in T cells selectively abrogated T cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased T cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating T homeostasis, which can be targeted to enhance T cell function in infection and following vaccination.