Fig. 2.

Targets of GR for immunomodulation. Hormone-activated GR is able to negatively regulate the activity of various other DNA-bound transcription factors, including among others NF-κB, CREB, IRF3, NFAT, STAT, T-Bet, GATA-3, and AP-1, via the transrepression mechanism or so-called tethering mechanism (factors inside circle). For AP-1, it has been described that GR can either negatively or positively influence its activity, depending on the composition of this dimer (see text for details). The pleiotropic GR is further capable of exerting its immune system modulatory effects through additional mechanisms (events depicted outside the circle). pol II, RNA polymerase II; TCR, T cell receptor. Arrow, Activating signal; blocked arrow, inhibitory signal; round arrow, modulatory signal, which can be either activating or inhibitory depending on the context, e.g. the loss of a coactivator or the recruitment of a corepressor molecule.