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Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease

Author

Listed:
  • Tingting Liu

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Zhenzhen Wang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences
    Shandong University)

  • Xiaotong Xue

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Zhe Wang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Yuan Zhang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Zihao Mi

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Qing Zhao

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Lele Sun

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Chuan Wang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Peidian Shi

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Gongqi Yu

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Meng Wang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Yonghu Sun

    (Shandong First Medical University
    Shandong Academy of Medical Sciences)

  • Fuzhong Xue

    (Shandong University)

  • Hong Liu

    (Shandong First Medical University
    Shandong Academy of Medical Sciences
    Shandong First Medical University and Shandong Academy of Medical Sciences)

  • Furen Zhang

    (Shandong First Medical University
    Shandong Academy of Medical Sciences
    Shandong First Medical University and Shandong Academy of Medical Sciences
    Shandong University of Traditional Chinese Medicine)

Abstract

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.

Suggested Citation

  • Tingting Liu & Zhenzhen Wang & Xiaotong Xue & Zhe Wang & Yuan Zhang & Zihao Mi & Qing Zhao & Lele Sun & Chuan Wang & Peidian Shi & Gongqi Yu & Meng Wang & Yonghu Sun & Fuzhong Xue & Hong Liu & Furen Z, 2024. "Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50283-3
    DOI: 10.1038/s41467-024-50283-3
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    References listed on IDEAS

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