Single-Cell Transcriptomes and Immune Repertoires Reveal the Cell State and Molecular Changes in Pemphigus Vulgaris

Abstract

ABSTRACTThe etiology and pathogenesis of pemphigus vulgaris (PV) are closely related to both immune cells and epithelial cells, but the specific subtypes of immune cells involved in PV and their roles are not yet fully understood. Additionally, the specific functions and mechanisms of first-line treatment glucocorticoids on cell types of PV remain to be elucidated. We performing 5’ single-cell RNA sequencing, combined with V(D)J enrichment on buccal mucosal lesions and peripheral blood samples from treatment-naïve patients with PV, in conjunction with post-treatment peripheral blood samples obtained after oral prednisone treatment. Our findings suggest that IL-1α signaling pathway, myeloid antigen presenting cells, inflammatory CD8+ Trm, and dysfunctional CD4+ Treg are crucial in PV. Our results were also supported by immunohistochemical assays. Furthermore, our results show that prednisone has a significant impact on monocytes and MAIT, but a limited effect on CD4+ Treg. Finally, we provide CDR3 amino acid sequence data of BCR that may be used as therapeutic targets. In conclusion, this study provides a comprehensive understanding of PV, particularly in the mucosal-dominant type, and the effect of GCs on PV, which could effectively lead to the development of new therapeutic strategies.