Autocrine VEGF-B signaling maintains lipid synthesis and mitochondrial fitness to support T cell immune responses.
J Clin Invest
; 134(16)2024 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-39145452
ABSTRACT
T cells rewire their metabolic activities to meet the demand of immune responses, but how to coordinate the immune response by metabolic regulators in activated T cells is unknown. Here, we identified autocrine VEGF-B as a metabolic regulator to control lipid synthesis and maintain the integrity of the mitochondrial inner membrane for the survival of activated T cells. Disruption of autocrine VEGF-B signaling in T cells reduced cardiolipin mass, resulting in mitochondrial damage, with increased apoptosis and reduced memory development. The addition of cardiolipin or modulating VEGF-B signaling improved T cell mitochondrial fitness and survival. Autocrine VEGF-B signaling through GA-binding protein α (GABPα) induced sentrin/SUMO-specific protease 2 (SENP2) expression, which further de-SUMOylated PPARγ and enhanced phospholipid synthesis, leading to a cardiolipin increase in activated T cells. These data suggest that autocrine VEGF-B mediates a signal to coordinate lipid synthesis and mitochondrial fitness with T cell activation for survival and immune response. Moreover, autocrine VEGF-B signaling in T cells provides a therapeutic target against infection and tumors as well as an avenue for the treatment of autoimmune diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T
/
Cardiolipinas
/
Transducción de Señal
/
Comunicación Autocrina
/
Factor B de Crecimiento Endotelial Vascular
/
Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Clin Invest
Año:
2024
Tipo del documento:
Article