title: Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells.
abstract: Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with T helper type 1-inducing activity. However, subsequent work has demonstrated that mice deficient in IL-27 receptor (IL-27R alpha) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27R alpha-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells. IL-27 acted directly on effector T cells to suppress the development of IL-17-producing T helper cells mediated by IL-6 and transforming growth factor-beta. This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon-gamma. Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation.
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California 94080, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Batten
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Sothy
authors.initials: S
authors.lastname: Yi
authors.forename: Noelyn M
authors.initials: NM
authors.lastname: Kljavin
authors.forename: Dimitry M
authors.initials: DM
authors.lastname: Danilenko
authors.forename: Sophie
authors.initials: S
authors.lastname: Lucas
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: Nico
authors.initials: N
authors.lastname: Ghilardi
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma