Single-cell transcriptome analysis reveals cellular heterogeneity in the aortas of Takayasu arteritis.

OBJECTIVES: Takayasu arteritis (TAK) is an inflammatory vasculitis that affects the aorta and its primary branches. The pathogenesis of TAK remains elusive, yet identifying key cell types in the aorta of TAK patients is crucial for uncovering cellular heterogeneity and discovering potential therapeutic targets. METHODS: This study utilized single-cell transcriptome analysis on aortic specimens from three TAK patients, with control data sourced from a publicly available database (GSE155468). Additionally, bulk RNA sequencing was performed on peripheral CD4 + and CD8 + T cells from eight TAK patients and eight matched healthy volunteers. All participants were recruited at Anzhen Hospital, Capital Medical University, China, between January 2020 and December 2023. RESULTS: Single-cell transcriptome analysis identified 11 predominant cell types in aortic tissues, with notable differences in proportions between TAK patients and controls. T cells, B cells, macrophages, smooth muscle cells (SMCs), and fibroblasts exhibited subtype-specific gene expression signatures, with notable changes in interactions between T cells, B cells, and monocyte-macrophages, highlighting their active involvement in the pathogenesis of TAK. Bulk RNA-Seq analysis of peripheral blood T cells from TAK patients showed an upregulation of complement system genes, underscoring the significance of the complement signaling pathway in TAK's immunopathogenesis. CONCLUSION: The findings underscore the active involvement of various immune and structural cells in the aortic tissues of TAK patients and reveal the presence of the complement signaling pathway in peripheral blood T cells. These insights are instrumental for identifying novel therapeutic targets and developing robust disease monitoring methods for TAK.