澳大利亚昆士兰大学Di Yu、华中科技大学Zheng Liu等研究人员合作发现，硒-GPX4信号轴保护滤泡辅助T细胞免受铁死亡影响。2021年8月19日，《自然—免疫学》杂志在线发表了这项成果。

研究人员发现，滤泡辅助T（T_FH）细胞显示出强化的脂质过氧化和线粒体形态的改变，类似于铁死亡的特征，这是一种程序性细胞死亡的形式，由铁依赖的脂质过氧化积累驱动。谷胱甘肽过氧化物酶4（GPX4）是主要的脂质过氧化清除剂，是T_FH细胞生存的必要条件。T细胞中GPX4的缺失会选择性地消除T_FH细胞和免疫小鼠的生发中心反应。补硒增强了GPX4在T细胞中的表达，增加了T_FH细胞的数量，促进了免疫小鼠和年轻成年人在接种流感疫苗后的抗体反应。

这些研究结果揭示了硒-GPX4-铁死亡信号轴在调节T_FH平衡中的核心作用，可以作为靶标来提高T_FH细胞在感染和疫苗接种后的功能。

据介绍，T_FH细胞是CD4⁺T细胞的一个特殊亚群，主要支持生发中心反应，在那里产生高亲和力和长效体液免疫。T_FH细胞的生存调节仍然不清楚。

附：英文原文

Title: Selenium–GPX4 axis protects follicular helper T cells from ferroptosis

Author: 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

Issue&Volume: 2021-08-19

Abstract: Follicular helper T (TFH) 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 TFH cell survival remains unclear. Here we report that TFH 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 TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH 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 TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.

DOI: 10.1038/s41590-021-00996-0

Source: https://www.nature.com/articles/s41590-021-00996-0