Published online before print July 8, 2008

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(Journal of Leukocyte Biology. 2008;84:644-650.)
© 2008 by Society for Leukocyte Biology

Glucocorticoids induce an activated, anti-inflammatory monocyte subset in mice that resembles myeloid-derived suppressor cells

Georg Varga^*,,1, Jan Ehrchen^*,,1, Athanasios Tsianakas^*,, Klaus Tenbrock^*,, Anke Rattenholl, Stephan Seeliger, Matthias Mack, Johannes Roth^*, and Cord Sunderkoetter^*,,2

^* Institute of Immunology and Departments of
Dermatology and
Pediatrics, University of Muenster, Muenster, Germany; and
Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany

² Correspondence: Department of Dermatology, University of Muenster, Von Esmarch Str. 58, Muenster D-48149, Germany. E-mail: cord.sunderkoetter{at}ukmuenster.de

ABSTRACT

Glucocorticoids (GC) are still the most widely used immunosuppressive agents in clinical medicine. Surprisingly, little is known about the mechanisms of GC action on monocytes, although these cells exert pro- and anti-inflammatory effects. We have shown recently that GC induce a specific monocyte phenotype with anti-inflammatory properties in humans. We now investigated whether this also applies for the murine system and how this subset would relate to recently defined murine subtypes. After treatment with dexamethasone for 48 h, monocytes up-regulated scavenger receptor CD163 and Gr-1, down-regulated CX₃CR1, and shared with human GC-treated monocytes functional features such as low adhesiveness but high migratory capacity. They specifically up-regulated anti-inflammatory IL-10, but not TGF-β, and in contrast to their human counterparts, they down-regulated IL-6. Although GC-induced monocytes down-regulated CX₃CR1, a distinctive marker for classical/proinflammatory human and murine monocytes (CX₃CR1^loCCR2⁺Ly6C^hi), they differed from this physiologically occurring subset, as they remained Ly6C^med and unactivated (CD62 ligand⁺⁺). In addition to their immunosuppressive effects, they were CD11b⁺Gr-1⁺ and expressed the IL-4R chain (CD124), a recently described, signature molecule of tumor-induced myeloid-derived suppressor cells (MDSC). We therefore generated murine MDSC in B16 melanoma-bearing mice and indeed found parallel up-regulation of CD11b⁺Gr-1⁺ and CD124 on GC-induced monocytes and MDSC. These data allow us to speculate that the GC-induced subtype shares with inflammatory monocytes the ability to migrate quickly into inflamed tissue, where they, however, exert anti-inflammatory effects and that similarities between GC-induced monocytes and MDSC may be involved in progression of some tumors observed in patients chronically treated with GC.

Key Words: IL-10 • CD124

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