title: IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells.
abstract: Group 2 innate lymphoid cells (ILC2) were recently characterized by their ability to produce significant amounts of type-2 signature cytokines and drive central beneficial and pathological features of type-2 immune responses. Although factors such as IL-33 and IL-25 were shown to have ILC2 activating capacity, it is not well understood, how ILC2 responses are regulated in vivo. Here we provide compelling evidence that IL-27-signalling directly inhibits ILC2 responses and reveal a novel mechanism for negative regulation of the innate arm of type-2 immunity. We demonstrate that IL-27-deficiency is linked to increased mucosal presence of ILC2 in a model of inflammatory lung disease. Moreover, IL-27-treatment inhibited ILC2 proliferation and cytokine production and significantly reduced their accumulation in vivo. During helminth infection, regulation of ILC2 by IL-27 directly impacted anti-parasitic immunity. Thus, therapeutic modulation of the IL-27/IL-27R axis may be relevant in a number of inflammatory conditions associated with dysregulated type-2 responses.
authors.affiliation: Department of Medicine 1, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Mchedlidze
authors.affiliation: Department of Medicine 1, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kindermann
authors.affiliation: Department of Infection Biology, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: A T
authors.initials: AT
authors.lastname: Neves
authors.affiliation: Department of Infection Biology, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Voehringer
authors.affiliation: Department of Medicine 1, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: M F
authors.initials: MF
authors.lastname: Neurath
authors.affiliation: Department of Medicine 1, University Medical Center, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wirtz
mesh_terms: D000818:Animals; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D007113:Immunity, Innate; D056747:Immunomodulation; D064094:Interleukin-27 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010271:Parasites / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D064094:Interleukin-27; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor