Wang Jianwei, Fan Hailang, Bao Zhengqing, Li Guizhong, Wang Lingyan, Zhang Dake
Urology Department, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 102200, People's Republic of China.
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education; Key Laboratory of Innovation and Transformation of Advanced Medical Devices, Ministry of Industry and Information Technology; National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering); School of Engineering Medicine, Beihang University, Beijing, 100191, People's Republic of China.
J Inflamm Res. 2025 Jan 7;18:283-299. doi: 10.2147/JIR.S481324. eCollection 2025.
Lichen sclerosus (LS) is a chronic inflammatory disease affecting skin and mucosal tissues, particularly external genitalia, with a risk of cancer. Its etiology is unknown, possibly involving immune dysregulation and inflammation.
Study used DNA methylation (DNAme) and single-cell RNA sequencing (scRNA-seq) to compare LS with normal skin. A detailed DNAme profile of LS was created, analyzing differentially methylated probes (DMPs) and cell type-specific DMPs. EpiSCORE deconvolution and immune infiltration analyses identified altered cell types in LS. Immunohistochemistry confirmed cellular changes. Enrichment analysis identified significantly altered pathways, and cell communication analysis described interactions among altered cell types in LS.
DNA methylation patterns generally distinguished LS from normal skin, with a few exceptions. Data analysis showed that T cells significantly increased and fibroblasts decreased in LS. Immunohistochemical staining confirmed the changes in T cells. Enrichment analysis of DMPs indicated significant impacts on fibroblast-related processes and key immune pathways. The COLLAGEN signal was the most prominent in the cell communication. The CD99-CD99 interaction was the strongest between T cells and fibroblasts.
Combining DNAme and scRNA-seq data revealed changes in cellular composition and immune pathways in LS, enhancing understanding of its pathogenesis and highlighting potential therapeutic targets and diagnostic markers.
硬化性苔藓（LS）是一种慢性炎症性疾病，可影响皮肤和黏膜组织，尤其是外生殖器，存在癌变风险。其病因不明，可能涉及免疫失调和炎症。
本研究使用DNA甲基化（DNAme）和单细胞RNA测序（scRNA-seq）来比较LS与正常皮肤。创建了LS的详细DNAme图谱，分析差异甲基化探针（DMP）和细胞类型特异性DMP。EpiSCORE反卷积和免疫浸润分析确定了LS中改变的细胞类型。免疫组织化学证实了细胞变化。富集分析确定了显著改变的通路，细胞通讯分析描述了LS中改变的细胞类型之间的相互作用。
DNA甲基化模式通常可将LS与正常皮肤区分开来，但有少数例外。数据分析表明，LS中T细胞显著增加，成纤维细胞减少。免疫组织化学染色证实了T细胞的变化。DMP的富集分析表明对成纤维细胞相关过程和关键免疫通路有显著影响。胶原蛋白信号在细胞通讯中最为突出。T细胞和成纤维细胞之间的CD99-CD99相互作用最强。
结合DNAme和scRNA-seq数据揭示了LS中细胞组成和免疫通路的变化，增强了对其发病机制的理解，并突出了潜在的治疗靶点和诊断标志物。
