Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
Front Immunol. 2019 Jul 16;10:1636. doi: 10.3389/fimmu.2019.01636. eCollection 2019.
Cutaneous lupus erythematosus can be a devastating painful and mutilating disease that is associated with an inflammatory response in the skin driven by type I interferon activation. Clearance defects in the extra- and intracellular space lead to an enhanced prevalence of nucleic acids that represent danger signals for the innate immune system. Self nucleic acids can stimulate DNA and RNA sensors that have originally evolved to ensure viral defense. Their activation can induce a type I interferon dominated response in resident skin cells, macrophages and dendritic cells that subsequently progresses to adaptive immune stimulation. The genetic exploration of rare monogenic type I interferon driven diseases helped to identify these pathogenic concepts. Based on a genetic susceptibility lupus patients are more vulnerable to environmental trigger factors such as UV-irradiation that can provoke inflammation with local tissue destruction and eventually systemic disease. Understanding of these pathogenic concepts is a prerequisite for development of targeted therapies.
皮肤狼疮红斑可以是一种破坏性的、疼痛的和致残的疾病，它与皮肤中的炎症反应有关，这种反应是由 I 型干扰素的激活驱动的。细胞外和细胞内空间的清除缺陷导致核酸的患病率增加，这些核酸代表了先天免疫系统的危险信号。自身核酸可以刺激最初为确保病毒防御而进化的 DNA 和 RNA 传感器。它们的激活可以诱导驻留皮肤细胞、巨噬细胞和树突状细胞中以 I 型干扰素为主导的反应，随后进展为适应性免疫刺激。对罕见的单基因 I 型干扰素驱动疾病的遗传探索有助于确定这些致病概念。基于遗传易感性，狼疮患者更容易受到环境触发因素（如紫外线辐射）的影响，这些触发因素可引发炎症，导致局部组织破坏，并最终导致全身性疾病。对这些致病概念的理解是开发靶向治疗的前提。
