Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.
Nat Immunol
; 22(9): 1127-1139, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34413521
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Selenio
/
Ferroptosis
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Fosfolípido Hidroperóxido Glutatión Peroxidasa
/
Células T Auxiliares Foliculares
Límite:
Adolescent
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Adult
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Animals
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Child
/
Female
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Humans
/
Male
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China