Selenium-GPX4 Axis Protects Follicular Helper T Cells from Ferroptosis

Overview

Journal Nat Immunol

Date 2021 Aug 20

PMID 34413521

Citations 132

Authors

Yin Yao

Zhian Chen

Hao Zhang

Cailing Chen

Ming Zeng

Joseph Yunis

Yunbo Wei

Yanmin Wan

Naiqi Wang

Mingzhe Zhou

Chao Qiu

Qunxiong Zeng

Hong Sheng Ong

Hao Wang

Fadzai Victor Makota

Yang Yang

Zhaohui Yang

Nan Wang

Jun Deng

Chao Shen

Yan Xia

Lin Yuan

Zhaoqin Lian

Yike Deng

Cuilian Guo

Ao Huang

Pengcheng Zhou

Haibo Shi

Weitian Zhang

Hongliang Yi

Dongmei Li

Ming Xia

Jing Fu

Ning Wu

Judy B de Haan

Nan Shen

Wenhong Zhang

Zheng Liu

Di Yu

Affiliations

Soon will be listed here.

Abstract

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.

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