Single-cell sequencing reveals distinct immune cell features in cutaneous lesions of pemphigus vulgaris and bullous pemphigoid

Clin Immunol. 2024 Jun:263:110219. doi: 10.1016/j.clim.2024.110219. Epub 2024 Apr 15.

Abstract

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

Keywords: Autoimmune bullous disease; Bullous pemphigoid; Pemphigus vulgaris; Single-cell RNA sequencing; VDJ.

MeSH terms

  • Aged
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Pemphigoid, Bullous* / genetics
  • Pemphigoid, Bullous* / immunology
  • Pemphigoid, Bullous* / pathology
  • Pemphigus* / genetics
  • Pemphigus* / immunology
  • Pemphigus* / pathology
  • Sequence Analysis, RNA
  • Single-Cell Analysis* / methods
  • Skin / immunology
  • Skin / pathology