title: IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice.
abstract: T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1β and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1β production and Th17 differentiation. IL-27Rα-/- T-cell receptor (TCR)β-/- recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Rα+/+ TCRβ-/- recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Rα-/- TCRβ-/- mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1β by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.
authors.affiliation: 1] Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA [2] Department of Molecular Medicine, Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Visperas
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Do
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bulek
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA [2] Department of Molecular Medicine, Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: B
authors.initials: B
authors.lastname: Min
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D064094:Interleukin-27 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000941:Antigens; D064094:Interleukin-27; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018123:Receptors, Interleukin