Advances in understanding the role of type I interferons in systemic lupus erythematosus.
Advances in understanding the role of type I interferons in systemic lupus erythematosus.
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DOI：
10.1097/bor.0000000000000087
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发表时间：
2014-09
影响因子：
5.1
通讯作者：
Crow MK
中科院分区：
文献类型：
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作者：
Crow MK
对先天性免疫系统激活和功能的遗传和分子基础的理解的进展支持了这样的假设，即I型干扰素（IFN-I），抗病毒宿主防御的必需介质，是系统性红斑狼疮（SLE）发病机制的主要贡献者。本文综述了最近的数据，支持的理论基础，治疗靶向干扰素-I途径在SLE。对细胞内在先天免疫系统激活机制的新见解，由内源性病毒样核酸驱动，并可能由环境应激源修饰，提供了一种诱导IFN-I的模型，该模型可能先于狼疮患者临床上明显的自身免疫。由激活内体Toll样受体的含核酸免疫复合物诱导的IFN-α产生的进一步扩增增强并维持免疫系统激活、自身免疫和组织损伤。如在持续病毒感染伴随持续产生IFN-I的小鼠研究中所证实的，阻断IFN-I途径可以逆转免疫失调和组织损伤，这是SLE免疫发病机制的基本特征。最近的研究进展已经确定了许多治疗靶点，并且正在研究与IFN-I途径相关的特定候选疗法。
Advances in understanding the genetic and molecular basis of innate immune system activation and function have supported the hypothesis that type I interferons (IFN-I), essential mediators of anti-viral host defense, are central contributors to the pathogenesis of systemic lupus erythematosus (SLE). This review addresses recent data that support the rationale for therapeutic targeting of the IFN-I pathway in SLE. New insights into mechanisms of cell-intrinsic innate immune system activation, driven by endogenous virus-like nucleic acids and potentially modified by environmental stressors, provide a model for induction of IFN-I that may precede clinically apparent autoimmunity in patients with lupus. Further amplification of IFN-α production, induced by nucleic acid-containing immune complexes that activate endosomal Toll-like receptors, augments and sustains immune system activation, autoimmunity and tissue damage. As demonstrated in murine studies of persistent virus infection accompanied by sustained production of IFN-I, blockade of the IFN-I pathway may reverse the immune dysregulation and tissue damage that are essential features of the immunopathogenesis of SLE. Recent research progress has identified numerous therapeutic targets, and specific candidate therapeutics relevant to the IFN-I pathway are under investigation.