Context-dependent regulation of follicular helper T cell survival

Zhian Chen; Naiqi Wang; Yin Yao; Di Yu

doi:10.1016/j.it.2022.02.002

Context-dependent regulation of follicular helper T cell survival

Trends Immunol. 2022 Apr;43(4):309-321. doi: 10.1016/j.it.2022.02.002. Epub 2022 Mar 4.

Authors

Zhian Chen¹, Naiqi Wang², Yin Yao³, Di Yu⁴

Affiliations

¹ The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: zhian.chen@uq.edu.au.
² The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
³ Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: di.yu@uq.edu.au.

PMID: 35249831
DOI: 10.1016/j.it.2022.02.002

Abstract

Follicular helper T (T_FH) cells are a specialized subset of CD4⁺ T cells that support germinal centers in producing high-affinity antibody-secreting and memory B cells in mammals and birds. Therefore, mechanisms have evolved to control the life and death of T_FH cells for balanced humoral immunity. Recent studies have collectively revealed at least two programmed cell death pathways, ferroptosis and pyroptosis, which govern T_FH cell survival under diverse physiopathological conditions including immunization, infection, gut homeostasis, and autoimmunity. We review major recent advances in our understanding of the context-dependent regulation of T_FH cell survival via cell death pathways that are closely connected with cellular metabolism. Such knowledge might be applied to inform new strategies aimed at modulating humoral immunity, potentially including enhancement of vaccine efficacies.

Keywords: Ferroptosis; Gpx4; P2X7R; Pyroptosis; T(FH) cells.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Autoimmunity
Cell Differentiation
Germinal Center*
Humans
Immunity, Humoral
Immunization
Mammals
T Follicular Helper Cells*
T-Lymphocytes, Helper-Inducer