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

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

  • Nat Commun. 2026 Mar 14;17(1):3962. doi: 10.1038/s41467-026-70506-z.
Rundong Jiang 1 2,  Rachael Bogle 1,  Xianying Xing 1,  Joseph Kirma 1,  Jennifer Fox 1,  Paul W Harms 1 3,  Tran Do 1,  Allison C Billi 1,  J Michelle Kahlenberg 4,  Robert L Modlin 5,  Rosane Teles 5,  Julie West 5,  Aaron Mangold 6,  Haihan Zhang 7,  Martin A Schneider 8,  Sandro Bruno 8,  Ben Roediger 8,  Georg Martiny-Baron 8,  Lam C Tsoi 1,  Feriel Hacini-Rachinel 8,  Till A Röhn 8,  Johann E Gudjonsson 9 10 11
Affiliations

Affiliations

  • 1 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • 2 Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA.
  • 3 Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • 4 Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA.
  • 5 Department of Dermatology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
  • 6 Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA.
  • 7 Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • 8 Immunology Disease Area, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
  • 9 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA. [email protected].
  • 10 Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA. [email protected].
  • 11 Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. [email protected].
PMID: 41832141 DOI: 10.1038/s41467-026-70506-z
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.

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