title: Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages.
abstract: Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine best known for its role in promoting the generation and function of neutrophils. G-CSF is also found to be involved in macrophage generation and immune regulation; however, its in vivo role in immune homeostasis is largely unknown. Here, we examined the role of G-CSF in dextran sulfate sodium (DSS)-induced acute colitis using G-CSF receptor-deficient (G-CSFR(-/-)) mice. Mice were administered with 1.5% DSS in drinking water for 5days, and the severity of colitis was measured for the next 5days. GCSFR(-/-) mice were more susceptible to DSS-induced colitis than G-CSFR(+/+) or G-CSFR(-/+) mice. G-CSFR(-/-) mice harbored less F4/80(+) macrophages, but a similar number of neutrophils, in the intestine. In vitro, bone marrow-derived macrophages prepared in the presence of both G-CSF and macrophage colony-stimulating factor (M-CSF) (G-BMDM) expressed higher levels of regulatory macrophage markers such as programmed death ligand 2 (PDL2), CD71 and CD206, but not in arginase I, transforming growth factor (TGF)-β, Ym1 (chitinase-like 3) and FIZZ1 (found in inflammatory zone 1), and lower levels of inducible nitric oxide synthase (iNOS), CD80 and CD86 than bone marrow-derived macrophages prepared in the presence of M-CSF alone (BMDM), in response to interleukin (IL)-4/IL-13 and lipopolysaccharide (LPS)/interferon (IFN)-γ, respectively. Adoptive transfer of G-BMDM, but not BMDM, protected G-CSFR(-/-) mice from DSS-induced colitis, and suppressed expression of tumor necrosis factor (TNF)-α, IL-1β and iNOS in the intestine. These results suggest that G-CSF plays an important role in preventing colitis, likely through populating immune regulatory macrophages in the intestine.
authors.affiliation: Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario N6G 2V4, Canada; Center for Human Immunology, University of Western Ontario, London, Ontario N6G 2V4, Canada.
authors.forename: Shahab
authors.initials: S
authors.lastname: Meshkibaf
authors.affiliation: Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario N6G 2V4, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Martins
authors.affiliation: Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario N6G 2V4, Canada.
authors.forename: Garth T
authors.initials: GT
authors.lastname: Henry
authors.affiliation: Department of Microbiology and Immunology and Infectious Diseases Research Group, Siebens-Drake Research Institute, University of Western Ontario, London, Ontario N6G 2V4, Canada; Center for Human Immunology, University of Western Ontario, London, Ontario N6G 2V4, Canada. Electronic address: sung.kim@schulich.uwo.ca.
authors.forename: Sung Ouk
authors.initials: SO
authors.lastname: Kim
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D016264:Dextran Sulfate; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006706:Homeostasis; D018793:Interleukin-13 / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II
keywords: Colitis; G-CSF; G-CSF receptor; Macrophage