Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection.
Cell Metab
; 28(6): 922-934.e4, 2018 12 04.
Article
em En
| MEDLINE
| ID: mdl-30174303
ABSTRACT
T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism. T cells lacking insulin receptor expression (LckCre+ Insrfl/fl) show reduced antigen-specific proliferation and compromised production of pro-inflammatory cytokines. In vivo, T cell-specific insulin receptor deficiency reduces T cell-driven colonic inflammation. In a model of severe influenza infection with A/PR8 (H1N1), lack of insulin receptor on T cells curtails antigen-specific immunity to influenza viral antigens. Mechanistically, insulin receptor signaling reinforces a metabolic program that supports T cell nutrient uptake and associated glycolytic and respiratory capacities. These data highlight insulin receptor signaling as an important node integrating immunometabolic pathways to drive optimal T cell effector function in health and disease.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor de Insulina
/
Ativação Linfocitária
/
Linfócitos T
/
Antígenos CD
/
Subpopulações de Linfócitos T
/
Influenza Humana
/
Vírus da Influenza A Subtipo H1N1
/
Imunidade Celular
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article