Nur77 Serves As a Molecular Brake of the Metabolic Switch During T Cell Activation to Restrict Autoimmunity

Significance The role of metabolic processes during T cell activation has been increasingly acknowledged, and recent data suggest an impact of T cell immunometabolism on T cell function and T cell-mediated autoimmunity. The factors regulating metabolic function in T cells are not clear, however. We identify the nuclear receptor Nur77 as central regulator of T cell immunometabolism, controlling oxidative phosphorylation and aerobic glycolysis during T cell activation. Functionally, Nur77 restricts murine and human T cell activation and proliferation and limits inflammation in autoimmune conditions in animal models of CNS autoimmunity, contact dermatitis, and arthritis. These findings identify Nur77 as a central regulator of T cell immunometabolism that restricts T cell-mediated autoimmunity, which might open up new avenues for a more tailored therapeutic approach.