Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity

M Liebmann, S Hucke, K Koch… - Proceedings of the …, 2018 - National Acad Sciences
M Liebmann, S Hucke, K Koch, M Eschborn, J Ghelman, AI Chasan, S Glander, M Schädlich…
Proceedings of the National Academy of Sciences, 2018National Acad Sciences
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 …
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.
National Acad Sciences