PPARß/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells.
Sci Immunol
; 9(98): eadn2717, 2024 Aug 23.
Article
em En
| MEDLINE
| ID: mdl-39178275
ABSTRACT
The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor ß/δ (PPARß/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8+ T cells. PPARß/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARß/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARß/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
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PPAR beta
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PPAR delta
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Camundongos Endogâmicos C57BL
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article