PRKAG2.2 is essential for FoxA1+ regulatory T cell differentiation and metabolic rewiring distinct from FoxP3+ regulatory T cells.
Sci Adv
; 9(51): eadj8442, 2023 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-38117896
ABSTRACT
Forkhead box A1 (FoxA1)+ regulatory T cells (Tregs) exhibit distinct characteristics from FoxP3+ Tregs while equally effective in exerting anti-inflammatory properties. The role of FoxP3+ Tregs in vivo has been challenged, motivating a better understanding of other Tregs in modulating hyperactive immune responses. FoxA1+ Tregs are generated on activation of the transcription factor FoxA1 by interferon-ß (IFNß), an anti-inflammatory cytokine. T cell activation, expansion, and function hinge on metabolic adaptability. We demonstrated that IFNß promotes a metabolic rearrangement of FoxA1+ Tregs by enhancing oxidative phosphorylation and mitochondria clearance by mitophagy. In response to IFNß, FoxA1 induces a specific transcription variant of adenosine 5'-monophosphate-activated protein kinase (AMPK) γ2 subunit, PRKAG2.2. This leads to the activation of AMPK signaling, thereby enhancing mitochondrial respiration and mitophagy by ULK1-BNIP3. This IFNß-FoxA1-PRKAG2.2-BNIP3 axis is pivotal for their suppressive function. The involvement of PRKAG2.2 in FoxA1+ Treg, not FoxP3+ Treg differentiation, underscores the metabolic differences between Treg populations and suggests potential therapeutic targets for autoimmune diseases.
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1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Proteínas Quinases Ativadas por AMP
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Dinamarca