Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Effects of GC have mainly been attributed to the suppression of T cells. Recently, several studies have indicated the role of dendritic cells (DC) in GC-mediated immunosuppression. We investigated the effect of GC on characteristics of DC. Given the crucial role of Toll-like receptor (TLR) triggering for the initiation of DC maturation program, we analyzed the expression of TLR2, 3, 4 by GC-treated DC. To extend our in vitro findings, we analyzed the distribution of DC subsets in the blood of patients treated with high-dose corticosteroids. DC differentiation in presence of GC was skewed to a qualitatively distinct population incapable of inducing an efficient immune response, whereas GC presence during the process of maturation significantly reduced DC IL-12 p70 and TNF production and T cell stimulatory function. Despite the fact that GC increased expression of TLR2, 3 and 4 on DC, their stimulation with TLR-derived signals did not induce maturation. Administration of high-dose GC to the patients with systemic autoimmunity induced a decrease of circulating myeloid DC and abrogated plasmacytoid DC. These findings provide further insights into the mechanisms of GC immunosuppressive functions and reveal additional mechanisms of their therapeutic efficiency.

Institute of Immunology Charles University 2nd Medical School 5 Uvalu 84 Prague 5 Czech Republic

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