Poster Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis and safeguards vaccine response (#112)

Di Yu 1 , Yin Yao 2 , Zhian Chen 1 , Hao Zhang 3 , Zheng Liu 2
  1. The University of Queensland Diamantina Institute, Woolloongabba, QLD, Australia
  2. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
  3. Shandong Analysis and Test Center, Qilu University of Technology, Jinan, China

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.