Oral Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis (#26)

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

Follicular helper T (TFH) cells are a specialised subset of CD4+ T cells essentially supporting the humoral immunity upon vaccination or infection. The mechanism controlling the survival of TFH cells has remained elusive. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis. Compared to other effector subsets of CD4+ T cells, TFH cells are particularly susceptible to ferroptosis. We found the deletion of glutathione peroxidase 4 (GPX4), the major ferroptosis scavenger, in T cells selectively abrogated TFH response in immunised mice. GPX4 represents a family of selenium-containing enzymes, we further showed selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers, and promoted antibody responses in immunised mice and young adults following influenza vaccination. Our findings reveal the central role of ferroptosis and the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH function in infection and following vaccination.