Department of Dermatology and Allergology, University of Bonn, Bonn, Germany.
J Invest Dermatol. 2011 Jan;131(1):133-40. doi: 10.1038/jid.2010.244. Epub 2010 Aug 19.
Type I IFNs (IFNα/β) have been shown to have a central role in the pathophysiology of lupus erythematosus (LE). The recently discovered type III IFNs (IFNλ1/IL29, IFNλ2/IL28a, IFNλ3/IL28b) share several functional similarities with type I IFNs, particularly in antiviral immunity. As IFNλs act primarily on epithelial cells, we investigated whether type III IFNs might also have a role in the pathogenesis of cutaneous LE (CLE). Our investigations demonstrate that IFNλ and the IFNλ receptor were strongly expressed in the epidermis of CLE skin lesions and related autoimmune diseases (lichen planus and dermatomyositis). Significantly enhanced IFNλ1 could be measured in the serum of CLE patients with active skin lesions. Functional analyses revealed that human keratinocytes are able to produce high levels of IFNλ1 but only low amounts of IFNα/β/γ in response to immunostimulatory nuclear acids, suggesting that IFNλ is a major IFN produced by these cells. Exposure of human keratinocytes to IFNλ1 induced the expression of several proinflammatory cytokines, including CXCL9 (CXC-motiv ligand 9), which drive the recruitment of immune cells and are associated with the formation of CLE skin lesions. Our results provide evidence for a role of type III IFNs in not only antiviral immunity but also autoimmune diseases of the skin.
I 型干扰素（IFNα/β）在红斑狼疮（LE）的病理生理学中起着核心作用。最近发现的 III 型干扰素（IFNλ1/IL29、IFNλ2/IL28a、IFNλ3/IL28b）在抗病毒免疫方面与 I 型 IFN 具有许多功能相似性。由于 IFNλ 主要作用于上皮细胞，我们研究了 III 型 IFN 是否也可能在皮肤红斑狼疮（CLE）的发病机制中发挥作用。我们的研究表明，IFNλ 和 IFNλ 受体在 CLE 皮肤病变和相关自身免疫性疾病（扁平苔藓和皮肌炎）的表皮中强烈表达。在有活动性皮肤病变的 CLE 患者的血清中可以测量到明显增强的 IFNλ1。功能分析显示，人角质形成细胞能够产生高水平的 IFNλ1，但对免疫刺激性核酸仅产生低水平的 IFNα/β/γ，这表明 IFNλ 是这些细胞产生的主要 IFN。IFNλ1 暴露于人角质形成细胞中会诱导几种促炎细胞因子的表达，包括 CXCL9（CXC 趋化因子配体 9），其驱动免疫细胞的募集，并与 CLE 皮肤病变的形成有关。我们的研究结果提供了证据，表明 III 型 IFN 在抗病毒免疫以及皮肤自身免疫性疾病中都发挥作用。
