期刊
EMBO MOLECULAR MEDICINE
卷 3, 期 6, 页码 348-361出版社
WILEY-BLACKWELL
DOI: 10.1002/emmm.201100142
关键词
colorectum; preinvasive tumors; TMIGD1; transcriptomics
资金
- Deutsche Forschungs-Gemeinschaft grant (DFG)
- European Commission
- Immunointervention Cluster of Excellence (ICE)
- Hellenic Ministry of Education [05AKMON105]
IL-28 (IFN-lambda) 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-gamma. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28R alpha(-/-) 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-gamma(-/-) 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.
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