Identification of CD8+ T cell PRDM1 in high-risk human plaques and its regulatory role in murine lesion development

摘要: Methods: We classified 43 human carotid arterial lesions into high-and low-risk plaques based on the presence/absence of intraplaque hemorrhages. RNA from these lesions was isolated and microarray gene expression data was obtained and analyzed by Weighted Gene Co-expression Network Analysis.Results: A strong T cell signalling signature was identified in high-versus low-risk plaques, influencing angiogenesis and interferon-related processes. Bayesian network inference, cell type deconvolution and single-cell RNA sequencing analysis revealed that the T cell-associated gene program was linked to effector-memory cytotoxic, CD8+ T cells. This gene program appeared driven by CD8+ T cell-related transcription factors, including RUNX3, IRF7 and most importantly PRDM1. To validate these findings, we demonstrated in a murine model that T cell PRDM1 plays a key role in plaque formation, as …