title: Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors.
abstract: 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.
authors.affiliation: Institute of Immunology, Charles University, 2nd Medical School, V Uvalu 84, Prague 5, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rozkova
authors.forename: Rudolf
authors.initials: R
authors.lastname: Horvath
authors.forename: Jirina
authors.initials: J
authors.lastname: Bartunkova
authors.forename: Radek
authors.initials: R
authors.lastname: Spisek
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D051193:Toll-Like Receptors; D003907:Dexamethasone; D011241:Prednisone; D008775:Methylprednisolone