IL-28A (IFN-l2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease

GSee accompanying Closeup by Michael R Edwards and Sebastian L Johnston http://dx.doi.org/10.1002/emmm.201100143 IL-28 (IFN-l) 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-g. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28Ra / 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 CD11cþ dendritic cell (DC) function to down-regulate OX40L, up-regulate IL12p70 and promote Th1 differentiation. Consistently, IL-28A-mediated protection was absent in IFN-g / mice or after IL-12 neutralization and could be adoptively transferred by IL-28A-treated CD11cþ cells. These data demonstrate a critical role of IL-28 cytokines in controlling T cell responses in vivo through the modulation of lung CD11cþ DC function in experimental allergic asthma.