Nature immunology · 2021
Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.
Предметные рубрики MeSH
AdolescentAdultAnimalsCell SurvivalChildFemaleFerroptosisGerminal CenterHomeostasisHumansImmunity, HumoralInfluenza VaccinesLipid PeroxidationMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaOvalbuminPhospholipid Hydroperoxide Glutathione PeroxidaseSeleniumT Follicular Helper CellsVaccinationYoung Adult