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.
The nerve growth factor IB (NGFIB) also known as Nur77 or NR4A1 (nuclear receptor subfamily 4 group A member 1) is an intracellular transcription factors. NGFIB is involved in cell cycle mediation, inflammation and apoptosis. The NGFIB protein plays a key role in mediating inflammatory responses in macrophages. In addition it appears to play a key role in the survival and death of cells as translocation of the protein from the nucleus to mitochondria induces apoptosis. In this study they focus on the influence of Nur77 in T cells.
Others (Lee SL; Wesselschmidt RL; Linette GP; Kanagawa O; Russell JH; Milbrandt J Science. 1995 Jul 28;269(5223):532-5) have reported T cells require the immediate-early gene NGFI-B (nur77) for T cell receptor (TCR)-mediated apoptosis, a model for negative selection of self-reactive T cells. TCR-mediated death was examined in mice bearing an NGFI-B loss-of-function mutation, either by administration of antibodies to CD3 (anti-CD3) or in two well-characterized transgenic models expressing self-reactive TCRs. Both the extent and the rate of thymocyte death were unimpaired. Anti-CD3-induced death was normal in CD4+ peripheral T cells, in which death is mediated predominantly by the Fas signaling pathway. Thus, no unique requirement for NGFI-B is observed for thymic or peripheral T cell death.