Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance.
Immunity
; 57(6): 1289-1305.e9, 2024 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-38772366
ABSTRACT
Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Linfócitos
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Tecido Adiposo
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Proteínas Serina-Treonina Quinases
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Receptor de Morte Celular Programada 1
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Homeostase
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Mitocôndrias
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Obesidade
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article