Work

Single-cell and spatial profiling reveal cDC2A-CXCL13+CD8+ T-epithelial cell crosstalk and cytotoxicity through TNFRSF9 in cutaneous and mucosal lichen planus

Year: 2026

Type: article

Abstract: Lichen planus (LP) is a chronic inflammatory disease of the skin and mucous membranes, marked by T cell infiltration and keratinocyte apoptosis. However, its immune microenvironment remains poorly understood. Using single-cell RNA sequencing, spatial transcriptomics, and proteomics on samples from 28 patients and 18 healthy controls, we identify elevated interferon (IFN) and cytotoxic signatures in CXCL13+CD8+ T cells in both cutaneous and mucosal LP, but not in lichen planopilaris. T cells expressing TNF and IFNG are spatially linked to epithelial cells through ligand-receptor interactions, correlating with inflammation. We identify cDC2A cells as key contributors, proximal to CXCL13+CD8+ T cells, serving as a major source of IL-15. CXCL13+CD8+ T cells express TNFRSF9 (4-1BB), which enhances their cytotoxic responses in the skin. In summary, our data reveal a critical role for cDC2A in driving CXCL13+CD8+ T–epithelial cytotoxicity in cutaneous and mucosal LP through TNFRSF9. The immune microenvironment of lichen planus remains poorly understood. By analyzing transcriptomics and proteomics data on samples from patients and healthy controls, the authors here show that cDC2A secreted IL-15 mediates CXCL13+CD8+ T to upregulate TNFRSF9 expression which contributes to epithelial cytotoxicity in cutaneous and mucosal LP.

Source: Nature Communications

DOI: 10.1038/s41467-026-70506-z