title: IL-27 Is Essential for Suppression of Experimental Allergic Asthma by the TLR7/8 Agonist R848 (Resiquimod).
abstract: Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell-driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production. Whereas R848 significantly reduced IL-5, IL-13, and IL-17, it induced IFN-γ and IL-27. Neutralization of IL-27 completely reversed the therapeutic effect of R848 in the experimental asthma model, demonstrating dependence of R848-mediated suppression on IL-27. In vitro, R848 induced production of IL-27 by murine alveolar macrophages and dendritic cells and enhanced expression of programmed death-ligand 1, whose expression on monocytes and dendritic cells has been shown to regulate peripheral tolerance in both murine and human studies. Moreover, in vitro IL-27 enhanced secretion of IFN-γ whereas it inhibited IL-5 and IL-13, demonstrating its direct effect on attenuating Th2 responses. Taken together, our study proves that R848-mediated suppression of experimental asthma is dependent on IL-27. These data provide evidence of a central role of IL-27 for the control of Th2-mediated allergic diseases.
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Member of the German Center for Lung Research, 30625 Hannover, Germany.
authors: Adan Chari
authors: 0000-0002-4693-0081
authors: AC
authors: Jirmo
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.
authors: Kathleen
authors: K
authors: Daluege
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Member of the German Center for Lung Research, 30625 Hannover, Germany.
authors: Christine
authors: C
authors: Happle
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.
authors: Melanie
authors: M
authors: Albrecht
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.
authors: Anna-Maria
authors: AM
authors: Dittrich
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.
authors: Mandy
authors: M
authors: Busse
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Member of the German Center for Lung Research, 30625 Hannover, Germany.
authors: Anika
authors: A
authors: Habener
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Member of the German Center for Lung Research, 30625 Hannover, Germany.
authors: Jelena
authors: 0000-0001-8509-6563
authors: J
authors: Skuljec
authors: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; and hansen.gesine@mh-hannover.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, Member of the German Center for Lung Research, 30625 Hannover, Germany.
authors: Gesine
authors: 0000-0001-5185-9454
authors: G
authors: Hansen
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D060890:B7-H1 Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000276:immunology; D051379:Mice; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C000611649:IFNG protein, mouse; C486767:Il27 protein, mouse; D007093:Imidazoles; D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; D008562:Membrane Glycoproteins; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D007371:Interferon-gamma; C402365:resiquimod