The kinase complex mTORC2 promotes the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.
Nat Immunol
; 23(2): 303-317, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34949833
ABSTRACT
Antigen-specific memory CD4+ T cells can persist and confer rapid and efficient protection from microbial reinfection. However, the mechanisms underlying the long-term maintenance of the memory CD4+ T cell pool remain largely unknown. Here, using a mouse model of acute infection with lymphocytic choriomeningitis virus (LCMV), we found that the serine/threonine kinase complex mammalian target of rapamycin complex 2 (mTORC2) is critical for the long-term persistence of virus-specific memory CD4+ T cells. The perturbation of mTORC2 signaling at memory phase led to an enormous loss of virus-specific memory CD4+ T cells by a unique form of regulated cell death (RCD), ferroptosis. Mechanistically, mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3ß kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4+ T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4), a major scavenger of lipid peroxidation. Thus, the mTORC2-AKT-GSK3ß axis functions as a key signaling hub to promote the longevity of virus-specific memory CD4+ T cells by preventing ferroptosis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
/
Diana Mecanicista del Complejo 2 de la Rapamicina
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Ferroptosis
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Memoria Inmunológica
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Longevidad
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Coriomeningitis Linfocítica
/
Virus de la Coriomeningitis Linfocítica
Límite:
Animals
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China