title: IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease.
abstract: IL-28 (IFN-λ) cytokines exhibit potent antiviral and antitumor function but their full spectrum of activities remains largely unknown. Recently, IL-28 cytokine family members were found to be profoundly down-regulated in allergic asthma. We now reveal a novel role of IL-28 cytokines in inducing type 1 immunity and protection from allergic airway disease. Treatment of wild-type mice with recombinant or adenovirally expressed IL-28A ameliorated allergic airway disease, suppressed Th2 and Th17 responses and induced IFN-γ. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28Rα(-/-) mice exacerbated allergic airway inflammation by augmenting Th2 and Th17 responses, and IgE levels. Central to IL-28A immunoregulatory activity was its capacity to modulate lung CD11c(+) dendritic cell (DC) function to down-regulate OX40L, up-regulate IL-12p70 and promote Th1 differentiation. Consistently, IL-28A-mediated protection was absent in IFN-γ(-/-) mice or after IL-12 neutralization and could be adoptively transferred by IL-28A-treated CD11c(+) cells. These data demonstrate a critical role of IL-28 cytokines in controlling T cell responses in vivo through the modulation of lung CD11c(+) DC function in experimental allergic asthma.
authors.affiliation: Center for Immunology and Transplantation, Biomedical Research Foundation Academy of Athens, Athens, Greece.
authors.forename: Ourania
authors.initials: O
authors.lastname: Koltsida
authors.forename: Michael
authors.initials: M
authors.lastname: Hausding
authors.forename: Athanasios
authors.initials: A
authors.lastname: Stavropoulos
authors.forename: Sonja
authors.initials: S
authors.lastname: Koch
authors.forename: George
authors.initials: G
authors.lastname: Tzelepis
authors.forename: Caroline
authors.initials: C
authors.lastname: Ubel
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Kotenko
authors.forename: Paschalis
authors.initials: P
authors.lastname: Sideras
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.forename: Marcus
authors.initials: M
authors.lastname: Tepe
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Klucher
authors.forename: Sean E
authors.initials: SE
authors.lastname: Doyle
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
authors.forename: Evangelos
authors.initials: E
authors.lastname: Andreakos
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D053278:OX40 Ligand / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D053278:OX40 Ligand; D011994:Recombinant Proteins; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda