IL‐28A (IFN‐λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease
Open Access
- 3 May 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 3 (6), 348-361
- https://doi.org/10.1002/emmm.201100142
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. →See accompanying Closeup by Michael R Edwards and Sebastian L Johnston http://dx.doi.org/10.1002/emmm.201100143Keywords
This publication has 36 references indexed in Scilit:
- Development of Allergen-Induced Airway Inflammation in the Absence of T-bet Regulation Is Dependent on IL-17The Journal of Immunology, 2009
- IFN-λ1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cellsBlood, 2009
- House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cellsNature Medicine, 2009
- Type III IFN‐λ mRNA expression in sputum of adult and school‐aged asthmaticsClinical & Experimental Allergy, 2008
- An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral ActivityThe Journal of Immunology, 2008
- Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytesHepatology, 2006
- Role of deficient type III interferon-λ production in asthma exacerbationsNature Medicine, 2006
- A stage-specific functional role of the leucine zipper transcription factor c-Maf in lung Th2 cell differentiationEuropean Journal of Immunology, 2004
- IL-6 Production by Pulmonary Dendritic Cells Impedes Th1 Immune ResponsesThe Journal of Immunology, 2003
- T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus ProductionThe Journal of Experimental Medicine, 1999