Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors

• Published in: Clinical Immunology Vol. 120; no. 3; pp. 260 - 271
• Main Authors: Rozkova, Daniela, Horvath, Rudolf, Bartunkova, Jirina, Spisek, Radek
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.09.2006; Elsevier
• Subjects: Antigen Presentation - drug effects; Antigen Presentation - immunology; Arthritis, Juvenile - blood; Arthritis, Juvenile - drug therapy; Arthritis, Juvenile - immunology; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - immunology; Child; Corticosteroids; Cytokines - immunology; Dendritic cell; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucocorticoids - pharmacology; High-dose corticosteroids; Humans; Immunopathology; Immunophenotyping; Immunosuppressive therapy; Lymphocyte Activation - drug effects; Male; Medical sciences; Methylprednisolone - pharmacology; Prednisone - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Toll-Like Receptors - biosynthesis; Toll-Like Receptors - genetics; Toll-Like Receptors - immunology; Toll-like receptors, maturation; CD40L; Dendritic cell; Corticosteroids; APC; High-dose corticosteroids; PAMPs; Poly (I:C); Immunosuppressive therapy; Toll-like receptors, maturation; DC; Immunopathology; Corticosteroid; maturation; Immunology; Antigen presenting cell; Dendritic cell; Corticosteroids; Immunosuppressive therapy; High-dose corticosteroids; Toll-like receptors; Toll like receptor; Immunosuppressive agent; Cell differentiation; High dose; Glucocorticoid
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2006.04.567

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.