Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by impaired immune tolerance, resulting in the generation of pathogenic autoantibodies and immune complexes. Although autoreactive B lymphocytes have been the first targets for biologic therapies in SLE, the importance of the innate immune system, and in particular, pathways involved in interferon (IFN) signaling, has emerged. There are now data supporting a central role for a plasmacytoid dendritic cell-derived type I IFN pathway in SLE, with a number of biologic therapeutics and small-molecule inhibitors undergoing clinical trials. Monoclonal antibodies targeting IFN-α have completed phase II clinical trials, and an antibody against the type I IFN receptor is entering a phase III trial. However, other IFNs, such as IFN gamma, and the more recently discovered type III IFNs, are also emerging as targets in SLE; and blockade of upstream components of the IFN signaling pathway may enable inhibition of more than one IFN subtype. In this review, we discuss the current understanding of IFNs in SLE, focusing on emerging therapies.

中文翻译：

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SLE 的靶向治疗：调节干扰素途径的新兴策略。


系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病，其特征是免疫耐受受损，导致致病性自身抗体和免疫复合物的产生。尽管自身反应性 B 淋巴细胞已成为 SLE 生物治疗的首要目标，但先天免疫系统，特别是干扰素 (IFN) 信号传导通路的重要性已经显现。现在有数据支持浆细胞样树突状细胞衍生的 I 型 IFN 通路在 SLE 中的核心作用，许多生物疗法和小分子抑制剂正在进行临床试验。针对IFN-α的单克隆抗体已完成II期临床试验，针对I型IFN受体的抗体正在进入III期试验。然而，其他干扰素，如干扰素γ和最近发现的III型干扰素，也正在成为系统性红斑狼疮的靶点；干扰素信号通路上游成分的阻断可能能够抑制不止一种干扰素亚型。在这篇综述中，我们讨论了目前对干扰素治疗系统性红斑狼疮的认识，重点关注新兴疗法。