IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease

Ourania Koltsida, Michael Hausding, Athanasios Stavropoulos, Sonja Koch, George Tzelepis, Caroline Übel, Sergei V. Kotenko, Paschalis Sideras, Hans A. Lehr, Marcus Tepe, Kevin M. Klucher, Sean E. Doyle, Markus F. Neurath, Susetta Finotto, Evangelos Andreakos

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)348-361
Number of pages14
JournalEMBO Molecular Medicine
Volume3
Issue number6
DOIs
StatePublished - Jun 2011

All Science Journal Classification (ASJC) codes

  • Molecular Medicine

Keywords

  • Adaptive immunity
  • Allergic asthma
  • Inflammation

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