Effects of glucocorticoids on STAT4 activation in human T cells are stimulus-dependent.

Glucocorticoids affect the immune sys- tem by a number of mechanisms, including modu- lation of cytokine production in lymphocytes. Glu- cocorticoids suppress T helper cell type 1 immune responses by decreasing the ability of T cells to respond to interleukin (IL)-12, a major inducer of interferon (IFN)-. IFN- increases the expression of the anti-inflammatory cytokine IL-10 and sup- presses IL-12. Signaling pathways through IFN- and the IL-12 receptor (IL-12R) involve activation by phosphorylation of signal transducer and acti- vator of transcription 4 (STAT4). Our aim was to investigate the effects of dexamethasone on STAT4 activation by IFN- and IL-12 in human T cell blasts. We report that dexamethasone decreases IL-12-induced STAT4 phosphorylation and IFN- production and enhances IFN--induced STAT4 activation and IL-10 production. These effects are associated with a down-regulation of IL-12R1 ex- pression but an up-regulation of IFN-R. These results indicate that the effect of glucocorticoids on the STAT4 signaling pathway depends on the stim- ulus activating that pathway. J. Leukoc. Biol. 80: 133-144; 2006.