The Interplay between the Glucocorticoid Receptor Activity and post-Translational Modifications in the Immune and Neuroendocrine Systems

Glucocorticoids (GCs), the most downstream effectors of the hypothalamic-pituitary-adrenal (HPA) axis, are key mediators in the interaction between immune and neuroendocrine systems. They exert their biological actions mainly through binding to their intracellular receptor, the glucocorticoid receptor (GR), which in turn influences gene expression by interacting with transcription factors and/or coregulators. GR abnormal function has been extensively associated to stress-related disorders, inflammatory and autoimmune diseases. Therefore, modulating GR activity is critical to overcome pathological conditions. The final outcome of GCs actions in the immune and neuroendocrine systems is regulated at multiple levels, including post-translational modifications (PTMs) of GR as well as of protein complexes involved in GR signaling. Understanding the influence of PTMs on the molecular mechanisms involved in GR signaling is thus of utmost importance in the search for therapeutic strategies aimed at modulating GR responses under pathophysiological circumstances, and to understand the neuroimmune circuits.