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<p>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<sup>+</sup>CD8<sup>+</sup> 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<sup>+</sup>CD8<sup>+</sup> T cells, serving as a major source of IL-15. CXCL13<sup>+</sup>CD8<sup>+</sup> 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<sup>+</sup>CD8<sup>+</sup> T–epithelial cytotoxicity in cutaneous and mucosal LP through TNFRSF9.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月14日

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  • Rundong Jiang,
  • Rachael Bogle,
  • Xianying Xing,
  • Joseph Kirma,
  • Jennifer Fox,
  • Paul W. Harms,
  • Tran Do,
  • Allison C. Billi,
  • J. Michelle Kahlenberg,
  • Robert L. Modlin,
  • Rosane Teles,
  • Julie West,
  • Aaron Mangold,
  • Haihan Zhang,
  • Martin A. Schneider,
  • Sandro Bruno,
  • Ben Roediger,
  • Georg Martiny-Baron,
  • Lam C. Tsoi,
  • Feriel Hacini-Rachinel,
  • Till A. Röhn,
  • Johann E. Gudjonsson

摘要

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.