title: GM-CSF mediates autoimmunity by enhancing IL-6-dependent Th17 cell development and survival.
abstract: Granulocyte macrophage-colony stimulating factor (GM-CSF) is critically involved in development of organ-related autoimmune inflammatory diseases including experimental allergic encephalitis and collagen-induced arthritis. Roles of GM-CSF in the initiation and in the effector phase of the autoimmune response have been proposed. Our study was designed to investigate the mechanisms of GM-CSF in autoimmunity using a model of autoimmune heart inflammatory disease (myocarditis). The pathological sequel after immunization with heart myosin has been shown previously to depend on IL-1, IL-6, IL-23, and IL-17. We found that innate GM-CSF was critical for IL-6 and IL-23 responses by dendritic cells and generation of pathological Th17 cells in vivo. Moreover, GM-CSF promoted autoimmunity by enhancing IL-6-dependent survival of antigen specific CD4(+) T cells. These results suggest a novel role for GM-CSF in promoting generation and maintenance of Th17 cells by regulation of IL-6 and IL-23 in vivo.
authors.affiliation: Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, 8952 Zürich, Switzerland.
authors.forename: Ivo
authors.initials: I
authors.lastname: Sonderegger
authors.forename: Giandomenica
authors.initials: G
authors.lastname: Iezzi
authors.forename: Reinhard
authors.initials: R
authors.lastname: Maier
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Kurrer
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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