Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity.
Proc Natl Acad Sci U S A
; 115(34): E8017-E8026, 2018 08 21.
Article
en En
| MEDLINE
| ID: mdl-30072431
ABSTRACT
T cells critically depend on reprogramming of metabolic signatures to meet the bioenergetic demands during activation and clonal expansion. Here we identify the transcription factor Nur77 as a cell-intrinsic modulator of T cell activation. Nur77-deficient T cells are highly proliferative, and lack of Nur77 is associated with enhanced T cell activation and increased susceptibility for T cell-mediated inflammatory diseases, such as CNS autoimmunity, allergic contact dermatitis and collagen-induced arthritis. Importantly, Nur77 serves as key regulator of energy metabolism in T cells, restricting mitochondrial respiration and glycolysis and controlling switching between different energy pathways. Transcriptional network analysis revealed that Nur77 modulates the expression of metabolic genes, most likely in close interaction with other transcription factors, especially estrogen-related receptor α. In summary, we identify Nur77 as a transcriptional regulator of T cell metabolism, which elevates the threshold for T cell activation and confers protection in different T cell-mediated inflammatory diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Consumo de Oxígeno
/
Activación de Linfocitos
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Linfocitos T
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Autoinmunidad
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Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares
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Mitocondrias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania