title: Immune suppression via glucocorticoid-stimulated monocytes: a novel mechanism to cope with inflammation.
abstract: Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work revealed that GCs induced a stable anti-inflammatory phenotype in monocytes, the GC-stimulated monocytes (GCsMs) that we exploited for targeted GC-mediated therapeutic effects. We demonstrate that GCsMs interact with T cells in suppressing proliferation, as well as cytokine release of CD8(+) and, especially, CD4(+) T cells in vitro, and that they support generation of Foxp3(+) cells. Therefore, we tested their immunosuppressive potential in CD4(+) T cell-induced colitis in vivo. We found that injection of GCsMs into mice with severe colitis abolished the inflammation and resulted in significant clinical improvement within a few days. T cells recovered from GCsM-treated mice exhibited reduced secretion of proinflammatory cytokines IFN-γ and IL-17. Furthermore, clusters of Foxp3(+) CD4(+) T cells were detectable at local sites of inflammation in the colon. Thus, GCsMs are able to modify T cell responses in vitro and in vivo, as well as to downregulate and clinically cure severe T cell-mediated colitis.
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany; Pediatric Rheumatology and Immunology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Georg
authors.initials: G
authors.lastname: Varga
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Jan
authors.initials: J
authors.lastname: Ehrchen
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Anne
authors.initials: A
authors.lastname: Brockhausen
authors.affiliation: Pediatric Rheumatology and Immunology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Toni
authors.initials: T
authors.lastname: Weinhage
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Nadine
authors.initials: N
authors.lastname: Nippe
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Belz
authors.affiliation: Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Athanasios
authors.initials: A
authors.lastname: Tsianakas
authors.affiliation: Department of Medicine B, University of Muenster, 48149 Muenster, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Ross
authors.affiliation: Department of Medicine B, University of Muenster, 48149 Muenster, Germany;
authors.forename: Dominik
authors.initials: D
authors.lastname: Bettenworth
authors.affiliation: Institute of Pathology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Marc
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Ralph
authors.initials: R
authors.lastname: Lippe
authors.affiliation: Department of Pediatrics, University of Aachen, Rheinisch Westfälische Technische Hochschule, 52062 Aachen, Germany; and.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tenbrock
authors.affiliation: Department of Immunology, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: Institute of Immunology, University of Muenster, 48149 Muenster, Germany; Department of Dermatology, University of Muenster, 48149 Muenster, Germany;
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkötter
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D003092:Colitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000009:adverse effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; D005938:Glucocorticoids; D018836:Inflammation Mediators; D016753:Interleukin-10