Identification of a PRDM1-regulated T cell network to regulate T cell driving plaque inflammation in human and mouse atherosclerosis

Abstract T cells have a prominent role in the pathogenesis of atherosclerosis, although their exact function remains elusive. Here, we pursued network-driven approach to identify cell-associated gene programs driving transition from low- high-risk human plaques. In this study 43 carotid arterial plaques were collected and stratified based on absence (low-risk) or presence (high-risk) intraplaque haemorrhage (IPH). Lesion RNA was subjected microarray expression analysis analysed by Weighted Gene Co-expression Network Analysis (WGCNA). We identified co-expressed cluster displaying strong cell signalling signature high- versus low-risk plaque, which tightly connected subnetworks angiogenesis interferon-signalling. WGCNA-based Bayesian network inference, cell-type deconvolution single-cell revealed that program likely linked effector-memory cytotoxic CD8+ cells, underpinning central plaque destabilization. regulatory cell-related transcription factors, like PRDM1, regulating program. Moreover, demonstrated LDL receptor knockout mice with cell-specific Prdm1 deficiency, lack resulted larger, more advanced conclusion, our reveals PRDM1-regulated footprint atherosclerotic lesions murine development, thereby identifying as potential target for intervention adverse responses. Funding Acknowledgement Type funding sources: Public grant(s) – EU funding. Main source(s): The European Research Area Cardiovascular Diseases (ERA-CVD Dutch Heart Foundation)