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<p>Cutaneous lupus erythematosus (CLE) encompasses several autoimmune entities characterized by a T cell-rich infiltrate and alopecia. Here, we perform spatial transcriptomics across three mammalian species to characterize potential T cell-hair follicle communication pathways in the microanatomical niche. In mice, adoptive transfer of either autoreactive CD4 + /OT2 or CD8 + /OT1 T results in skin disease with 35% gene expression overlap. CD8 T cells specifically contribute to extracellular matrix reorganization. Digital spatial profiling of skin identifies CXCR3 ligands and IFN response genes in hair follicles, also conserved in pet dog and human Discoid lupus erythematosus (DLE) biopsies. Knock-out of CXCR3 on OT2 T cells alleviates skin disease in CLE mice. Moreover, B cell depletion in OT1 CLE recipient mice reduces skin disease scores as relevant to human B cell depletion therapies for lupus. Last, we identify <i>CFD</i> and <i>S100A8/9</i> as conserved targets that could be further explored through future veterinary and human trials.</p>

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Cross-species comparative spatial transcriptomics of hair follicle-T cell interactions identifies conserved drivers of cutaneous lupus erythematosus skin disease and associated hair loss

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Ümmügülsüm Yıldız-Altay,
  • Rutha Adhanom,
  • Warda Abdi,
  • Andrew Romasco,
  • Lauren You,
  • Nuha Salam,
  • Robert Li,
  • Haya Raef,
  • Yuying Zhang,
  • Elise Santacruz,
  • Katelin Murphy,
  • Saeed Shakiba,
  • Mridushi Daga,
  • Qi Tang,
  • Matthew Olivera,
  • Thomas Cicuto,
  • Floriane Bretheau,
  • Ann Marshak-Rothstein,
  • Michael D. Rosenblum,
  • Christina E. Baer,
  • Motahareh Arjomandnejad,
  • Allison Keeler,
  • Helen Bui,
  • Amanda Martinot,
  • Babak Shokrani,
  • Ramon Almela,
  • Angel S. Byrd,
  • Cheri Frey,
  • Jillian M. Richmond

摘要

Cutaneous lupus erythematosus (CLE) encompasses several autoimmune entities characterized by a T cell-rich infiltrate and alopecia. Here, we perform spatial transcriptomics across three mammalian species to characterize potential T cell-hair follicle communication pathways in the microanatomical niche. In mice, adoptive transfer of either autoreactive CD4 + /OT2 or CD8 + /OT1 T results in skin disease with 35% gene expression overlap. CD8 T cells specifically contribute to extracellular matrix reorganization. Digital spatial profiling of skin identifies CXCR3 ligands and IFN response genes in hair follicles, also conserved in pet dog and human Discoid lupus erythematosus (DLE) biopsies. Knock-out of CXCR3 on OT2 T cells alleviates skin disease in CLE mice. Moreover, B cell depletion in OT1 CLE recipient mice reduces skin disease scores as relevant to human B cell depletion therapies for lupus. Last, we identify CFD and S100A8/9 as conserved targets that could be further explored through future veterinary and human trials.