TY - JOUR
T1 - Glucocorticoid signaling: a nongenomic mechanism for T-cell immunosuppression
AU - Lowenberg, Mark
AU - Verhaar, Auke P.
AU - van den Brink, Gijs R.
AU - Hommes, Daniel W.
PY - 2007
Y1 - 2007
N2 - Glucocorticoids were long believed to exert their effects through transcriptional regulation of glucocorticoid-receptor target genes. However, there is accumulating evidence for nongenomic glucocorticoid-receptor-dependent modulation of signal transduction pathways. Here, we review rapid glucocorticoid activities and focus on a novel mechanism that underlies nongenomic glucocorticoid-induced immunosuppression in T cells. The findings demonstrate a physical and functional interaction between the glucocorticoid receptor and the T-cell receptor (TCR) complex. In its unligated state, the glucocorticoid receptor has an important role in TCR signaling but, after glucocorticoid-receptor-ligand binding (caused by short-term treatment with the synthetic glucocorticoid dexamethasone), the TCR complex is disrupted, leading to impaired TCR signaling. These data reveal a dichotomal functional role for glucocorticoid receptors: one in the cytosol as part of the TCR complex and the other as a nuclear regulator of gene transcription. Drugs that selectively target membrane-bound glucocorticoid receptors might represent a novel immunosuppressive approach
AB - Glucocorticoids were long believed to exert their effects through transcriptional regulation of glucocorticoid-receptor target genes. However, there is accumulating evidence for nongenomic glucocorticoid-receptor-dependent modulation of signal transduction pathways. Here, we review rapid glucocorticoid activities and focus on a novel mechanism that underlies nongenomic glucocorticoid-induced immunosuppression in T cells. The findings demonstrate a physical and functional interaction between the glucocorticoid receptor and the T-cell receptor (TCR) complex. In its unligated state, the glucocorticoid receptor has an important role in TCR signaling but, after glucocorticoid-receptor-ligand binding (caused by short-term treatment with the synthetic glucocorticoid dexamethasone), the TCR complex is disrupted, leading to impaired TCR signaling. These data reveal a dichotomal functional role for glucocorticoid receptors: one in the cytosol as part of the TCR complex and the other as a nuclear regulator of gene transcription. Drugs that selectively target membrane-bound glucocorticoid receptors might represent a novel immunosuppressive approach
U2 - https://doi.org/10.1016/j.molmed.2007.02.001
DO - https://doi.org/10.1016/j.molmed.2007.02.001
M3 - Review article
C2 - 17293163
SN - 1471-4914
VL - 13
SP - 158
EP - 163
JO - Trends in molecular medicine
JF - Trends in molecular medicine
IS - 4
ER -