Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Eur J Immunol. 2015 Jan;45(1):250-9. doi: 10.1002/eji.201444903. Epub 2014 Nov 10.
With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although the antiviral activity of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production.
随着人们对干扰素-α为基础的治疗方法的替代方案的兴趣日益增加，IFN-λ 在多种疾病中显示出了治疗潜力。尽管 IFN-λ 的抗病毒活性已得到广泛研究，但人们对其免疫功能以及与其他类型 IFN 的区别知之甚少。在这项研究中，我们研究了 IFN-λ 对原代人自然杀伤 (NK) 细胞的直接和间接作用。我们发现，与干扰素-α不同，由于 NK 细胞上缺乏 IFN-λ 受体链 1 (IFN-λR1)，IFN-λ 无法直接刺激 NK 细胞。然而，IFN-λ 与 TLR4 挑战联合使用，能够诱导单核细胞来源的巨噬细胞中产生选择的 IL-12 细胞因子家族成员。我们进一步表明，IFN-λ 通过巨噬细胞介导的 IL-12 产生，能够间接影响 NK 细胞，并最终诱导 IFN-γ 的产生。
