Early growth response transcription factors and the modulation of immune response: implications towards autoimmunity

Abstract

Early Growth Response (EGR) zinc finger transcription factors are induced under diverse mitogenic signals on different cell types such as lymphocytes. Their genetic expression does not require de novo protein synthesis, which suggests its role as immediate response mediators between cell surface receptor signaling and gene expression regulation. EGR factors are involved in modulating the immune response, by means of the induction of differentiation of lymphocyte precursors, activation of T and B cells, as well as their involvement in central and peripheral tolerance. The maturation state, particularly for B cells, and signaling through the T or B cell receptors seems to be quite relevant for the induction of the expression of these transcription factors. EGR-1 functions as a positive regulatory factor for B and T cells mediated by transcriptional regulation of key cytokines and costimulatory molecules, and its interaction with NFAT. On the opposite, EGR-2 and 3 act as negative regulators involved in anergy induction and apoptosis. EGR-2 and 3 deficiency has been related to the development of lupus like disease in murine models. The deficiency of these transcription factors has been associated to deficient Cbl-b expression, a resistant to anergy phenotype, and expansion of effector and activated T cells.