title: Altered gp130 signalling ameliorates experimental colitis via myeloid cell-specific STAT3 activation and myeloid-derived suppressor cells.
abstract: STAT3 regulates the expansion of myeloid-derived suppressor cells (MDSCs) during inflammation, infection and cancer. Hyperactivation of STAT3 in gp130(757F/F) mice is associated with protection from experimental colitis. This study determined mechanisms for this protection and compared this to mice with myeloid-specific STAT3-deficiency (LysMcre/STAT3(flox); gp130(757F/F) LysMcre/STAT3(flox)). Acute and chronic colitis was induced and colons were removed for histological, mRNA and protein analysis. Cell populations from spleen, mesenteric lymph node and colon were analyzed for different myeloid cell populations using flow cytometry. Functions of MDSCs and LPS-stimulated peritoneal macrophages were further characterized by in vitro and in vivo assays. Here we show that the resistance to experimental colitis in gp130(757F/F) mice is via myeloid-cell specific STAT3 activation, MDSC expansion and increased production of suppressive and protective cytokines.
authors: Gastrointestinal Research in Inflammation and Pathology, Infection and Immunity Research Theme, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne Medical School, Parkville, Victoria, Australia.
authors: Jan
authors: J
authors: Däbritz
authors: Gastrointestinal Research in Inflammation and Pathology, Infection and Immunity Research Theme, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne Medical School, Parkville, Victoria, Australia.
authors: Louise M
authors: LM
authors: Judd
authors: Gastrointestinal Research in Inflammation and Pathology, Infection and Immunity Research Theme, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors: Heather V
authors: HV
authors: Chalinor
authors: Gastrointestinal Research in Inflammation and Pathology, Infection and Immunity Research Theme, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne Medical School, Parkville, Victoria, Australia.
authors: Trevelyan R
authors: TR
authors: Menheniott
authors: Gastrointestinal Research in Inflammation and Pathology, Infection and Immunity Research Theme, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Melbourne Medical School, Parkville, Victoria, Australia.
authors: Andrew S
authors: AS
authors: Giraud
mesh_terms: D000818:Animals; D003092:Colitis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism / Q000473:pathology; D050822:Cytokine Receptor gp130 / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; C494200:Il6st protein, mouse; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130