Center for Immunology and Transplantation, Biomedical Research Foundation Academy of Athens, Athens, Greece.
EMBO Mol Med. 2011 Jun;3(6):348-61. doi: 10.1002/emmm.201100142. Epub 2011 May 3.
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.
IL-28（IFN-λ）细胞因子具有强大的抗病毒和抗肿瘤功能，但它们的全部活性仍知之甚少。最近，发现 IL-28 细胞因子家族成员在过敏性哮喘中显著下调。我们现在揭示了 IL-28 细胞因子在诱导 1 型免疫和预防过敏性气道疾病中的新作用。用重组或腺病毒表达的 IL-28A 治疗野生型小鼠可改善过敏性气道疾病，抑制 Th2 和 Th17 反应并诱导 IFN-γ。此外，在 IL-28Rα(-/-) 小鼠中阻断内源性 IL-28 细胞因子功能通过增强 Th2 和 Th17 反应和 IgE 水平加重过敏性气道炎症。IL-28A 免疫调节活性的核心是其调节肺 CD11c(+)树突状细胞 (DC) 功能的能力，可下调 OX40L，上调 IL-12p70 并促进 Th1 分化。一致地，IFN-γ(-/-) 小鼠或在 IL-12 中和后缺乏 IL-28A 介导的保护作用，并且可以通过 IL-28A 处理的 CD11c(+)细胞进行过继转移。这些数据表明，IL-28 细胞因子在通过调节实验性过敏性哮喘中的肺 CD11c(+)DC 功能来控制体内 T 细胞反应方面具有关键作用。
