Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to prevent autoinflammatory disease.

ABSTRACT: Foxp3⁺ T regulatory (T_reg) cells suppress immune cell activation and establish normal immune homeostasis. How T_reg cells maintain their identity is not completely understood. Here we show that Ndfip1, a coactivator of Nedd4-family E3 ubiquitin ligases, is required for T_reg cell stability and function. Ndfip1 deletion in T_reg cells results in autoinflammatory disease. Ndfip1-deficient T_reg cells are highly proliferative and are more likely to lose Foxp3 expression to become IL-4-producing T_H2 effector cells. Proteomic analyses indicate altered metabolic signature of Ndfip1-deficient T_reg cells and metabolic profiling reveals elevated glycolysis and increased mTORC1 signalling. Ndfip1 restricts T_reg<

SUBMITTER: Layman AAK 

PROVIDER: S-EPMC5465375 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature