Multiomics Analysis Reveals Distinct Changes in the Cellular Composition of Vulvar Lichen Sclerosus.

OBJECTIVE

This study aimed to investigate cellular composition and gene/pathway alterations in VLS tissue compared with normal skin using single-cell RNA sequencing (scRNA-seq) and lipid metabolomics.

METHODS

scRNA-seq was conducted on 4 VLS samples and self-control vulvar skin. Lipid metabolism analysis was performed on 15 VLS samples. Bioinformatics assessed cellular abundance, differentially expressed genes (DEGs), and functional pathways between VLS and normal tissues. DEGs were validated via immunofluorescence.

RESULTS

The authors found significant changes in cell-type abundance in the LS samples, with increased abundance of T cells, particularly the C01-GZMB/GZMK and C05-GNLY/XCL1 T cell subsets, and decreased abundance of fibroblasts, keratinocytes, and melanocytes. Furthermore, scRNA-seq data indicated distinct trends in the expression of key metabolic and inflammatory genes. Notably, lymphocyte-mediated immunity, leukocyte-mediated cytotoxicity, and cell-killing pathways were upregulated in the T cells of VLS, suggesting an ongoing inflammatory milieu. Cell communication analysis revealed an increase in the interactions among cell types, with the interaction intensity between T cells and fibroblasts showing the most pronounced increase. Immunofluorescence results revealed that GZMB and the pro-inflammatory factors, IFN-γ and TNF-β, were significantly increased in the VLS tissues. The epidermal keratin expression in the VLS tissue was abnormal, and the basal layer of the VLS tissue lost its normal single-layer structure, and the arrangement was disordered.

CONCLUSION

Cellular composition changes in VLS T cells lead to apoptosis of normal skin cells, contributing to skin tissue destruction and playing a critical role in the inflammatory development of the disease.