Immunopathogenesis of Lichen Planus
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摘要: 扁平苔藓是一种慢性、免疫介导的炎症性疾病，以苔藓样界面皮炎为特征。扁平苔藓发病是遗传易感性与环境因素交互作用的结果。免疫机制以T细胞介导为主：IFN-γ、TNF-α及IL-23/Th17轴驱动炎症，CD8+细胞毒性T细胞通过穿孔素/颗粒酶B及Fas/FasL途径诱导角质形成细胞凋亡；JAK-STAT信号通路及代谢异常进一步放大炎症。对LP病因学、免疫发病机制及临床关联进行系统综述，为精准分型与靶向治疗提供理论依据。Abstract: Lichen planus is a chronic, immune-mediated inflammatory disease characterized by lichenoid interface dermatitis. Its development results from interactions between genetic susceptibility and environmental factors. The immune mechanisms are predominantly T-cell mediated: IFN-γ, TNF-α, and the IL-23/Th17 axis drive inflammation, while CD8+cytotoxic T cells induce keratinocyte apoptosis via the perforin/granzyme B and Fas/FasL pathways. JAK-STAT signaling and metabolic abnormalities further amplify the inflammatory response. A systematic review of the etiology, immunopathogenesis, and clinical associations of LP provides a theoretical basis for precision subtyping and targeted therapy.
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Key words:
- Lichen planus /
- Immunity /
- Pathogenesis
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图 2 LP复杂炎症网络中包括的主要效应细胞和信号通路
注：遗传与环境因素驱动表皮基底细胞应激，激活pDC与真皮DC引发IL-12/23-Th1/Th17信号轴极化，并在CCL20/CXCL趋化因子受体轴的招募下靶向真皮，继而通过Th1/Th17协同活化CD8+T细胞，经由Fas-FasL通路及穿孔素/颗粒酶释放触发细胞毒性效应，最终诱导基底角质形成细胞凋亡，形成扁平苔藓样丘疹。
Figure 2. Major effector cells and signaling pathways involved in the complex inflammatory network of lichen planus
表 1 与LP相关的主要免疫细胞亚群及其功能
Table 1. Main immune cell subsets associated with LP and their functions
细胞类型 主要亚型/标记 病变中变化
（vs健康对照）核心功能与效应 关键分子 参考文献 树突状细胞 朗格汉斯细胞（CD1a+/CD207+）、髓系DC、浆细胞样DC 各亚型数量增加 抗原呈递，分泌IFN-α、IL-12、IL-23，启动Th1/Th17应答 CD1a，CD207，IFN-α，IL-12，IL-23 [50−53] 巨噬细胞 M1型、CD68+ 数量增加，聚集于基底膜附近（距表皮≤125μm） 分泌促炎因子及趋化因子，维持慢性炎症，介导CD8+T细胞趋化 TNF-α，IL-1β，CCL5，MMPs，MIP-1α/β（外泌体） [54−56] CD4+T细胞 Th1、Th17、Tfh 真皮浸润增加，CD4+/CD8+比值约1.75:1 分泌IFN-γ、IL-17等，辅助CD8+T细胞活化，促进慢性炎症及体液免疫 IFN-γ，IL-17，IL-22，IL-21 [60−62] CD8+T细胞 Tc1、Tc17、MAIT、γδT 表皮基底层浸润为主，随疾病进展增多 识别MHC-I呈递的抗原，通过穿孔素/颗粒酶B、FasL、TNF-α诱导角质形成细胞凋亡 穿孔素，颗粒酶B，颗粒溶素，FasL，IFN-γ [45，58−59] 调节性T细胞 FoxP3+Treg 病变组织及血液中比例升高（可占浸润细胞17.7%） 免疫抑制功能受损，可重编程为促炎表型（异常分泌IFN-γ、IL-17） FoxP3，IL-17（异常） [63−66] NK细胞 CD56dimCD16- 占皮肤LP浸润细胞约10% 产生TNF-α、IFN-γ、IL-17、IL-22，可能促进T细胞动员1 TNF-α，IFN-γ，IL-17，IL-22 [67−68] 角质形成细胞 基底角质形成细胞 凋亡增加（靶细胞） 通过MHC-I/II呈递抗原，分泌促炎因子，维持基底膜；被CTL诱导凋亡 MHC-I/II，IL-1β，IL-6，TNF-α，聚丝蛋白 [69−71] 肥大细胞 类胰蛋白酶/乳糜酶阳性 基底膜破坏区数量增加，60%呈脱颗粒状态 释放RANTES、蛋白酶等，激活MMPs，形成正反馈放大炎症 RANTES，类胰蛋白酶，乳糜酶，TNF-α [57] 中性粒细胞 多形核中性粒细胞 血清钙卫蛋白水平升高 形成NETs，N2表型可能参与OLP向鳞癌的恶性转化 钙卫蛋白，BAFF [72−73] 
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