Single-Cell RNA Sequencing + TCR Sequencing Reveal the Proportion and Characteristics of Dual TCR T Cells in Tertiary Lymphoid Structures in Pemphigus.

The origin, characteristics, and the effects/mechanisms of lymphocytes within tertiary lymphoid structures (TLSs) in pemphigus pathological skin tissue as well as their role in pemphigus pathogenesis remain unclear. Using single-cell RNA-sequencing and TCR-sequencing analysis, this study revealed that pemphigus TLSs (denoted as P_TLS) contain a higher proportion of dual TCR T cells than chronic idiopathic erythroderma and healthy control skin tissues. Notably, P_TLSs exhibit a unique enrichment of clonally expanded dual TCR CXCL13+CD4+ T cells, whereas the proportions of dual TCR regulatory T cells and dual TCR CD8+ T cells are reduced. However, CXCR5 is significantly upregulated in dual TCR regulatory T cells within P_TLSs. The dual TCR T cells within P_TLSs exhibit significant heterogeneity in their top 10 mRNA expressions compared with those in healthy control and chronic idiopathic erythroderma. For instance, P_TLS shows high expression of IL17F, among others. There is also substantial heterogeneity in shared CDR3 (complementarity determining region 3) sequences and V gene usage among single and dual TCR T cells across healthy control, P_TLS, and chronic idiopathic erythroderma tissues. These findings provide insights and a basis for further exploring TLS formation and the origin, effects, and mechanisms of potential novel T-cell subsets in pemphigus pathogenesis.