Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to prevent autoinflammatory disease.
Nat Commun
; 8: 15677, 2017 06 05.
Article
em En
| MEDLINE
| ID: mdl-28580955
ABSTRACT
Foxp3+ T regulatory (Treg) cells suppress immune cell activation and establish normal immune homeostasis. How Treg cells maintain their identity is not completely understood. Here we show that Ndfip1, a coactivator of Nedd4-family E3 ubiquitin ligases, is required for Treg cell stability and function. Ndfip1 deletion in Treg cells results in autoinflammatory disease. Ndfip1-deficient Treg cells are highly proliferative and are more likely to lose Foxp3 expression to become IL-4-producing TH2 effector cells. Proteomic analyses indicate altered metabolic signature of Ndfip1-deficient Treg cells and metabolic profiling reveals elevated glycolysis and increased mTORC1 signalling. Ndfip1 restricts Treg cell metabolism and IL-4 production via distinct mechanisms, as IL-4 deficiency does not prevent hyperproliferation or elevated mTORC1 signalling in Ndfip1-deficient Treg cells. Thus, Ndfip1 preserves Treg lineage stability and immune homeostasis by preventing the expansion of highly proliferative and metabolically active Treg cells and by preventing pathological secretion of IL-4 from Treg cells.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas de Transporte
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Linfócitos T Reguladores
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Inflamação
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article