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.
摘要：
大疱性类天疱疮（BP）和寻常型天疱疮（PV）是自身免疫性大疱性疾病（AIBD）的两种常见亚型。循环自身反应性免疫细胞对AIBD皮肤损伤的关键作用已得到广泛认可。然而，皮肤病变的免疫特征仍不清楚。这里,我们进行了单细胞RNA测序(scRNA-seq)和单细胞VDJ测序(scRNA-seq),以产生BP和PV皮损中细胞和T/B细胞克隆型的转录谱.我们发现NK&T的比例,巨噬细胞/树突状细胞，B细胞,肥大细胞在BP和PV病变中增加。然后，BP和PV细胞占所有骨髓细胞亚型的75％以上，CD4+T细胞亚型和CD8+T细胞亚型。引人注目的是，CD8+Trm被鉴定为在PV中扩展，并位于从CD8+Tm到CD8+Tem的伪时间轨迹的中间状态。有趣的是,CD8+Tem和CD4+Treg高表达耗竭相关基因，尤其是在BP病变中。此外，在BP和PV病变中还发现基质细胞与免疫细胞如B细胞和巨噬细胞/树突状细胞之间的细胞通讯增强.最后,与HC相比，在BP和PV的T细胞中观察到克隆扩增，而CD8+Trm代表所有T细胞亚型中超扩增TCR克隆的最高比例。我们的研究总体上描绘了皮肤病变的大型而全面的单细胞景观，并突出了BP和PV中的免疫细胞特征。这为进一步调查提供了潜在的研究目标。
