Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors
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...
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 120(2006), 3 vom: 15. Sept., Seite 260-71 |
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1. Verfasser: | |
Weitere Verfasser: | , , |
Format: | Aufsatz |
Sprache: | English |
Veröffentlicht: |
2006
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Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Cytokines Glucocorticoids Toll-Like Receptors Dexamethasone 7S5I7G3JQL Prednisone VB0R961HZT Methylprednisolone |
Zusammenfassung: | 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 |
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Beschreibung: | Date Completed 26.09.2006 Date Revised 09.04.2022 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |