Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques

Abstract

Tertiary lymphoid organs have been identified in the arterial adventitia in both mouse models of atherosclerosis and patients with atherosclerosis, yet their role in the disease remains insufficiently explored. Here we present a spatially resolved single-cell transcriptome atlas of human atherosclerotic plaques, identifying 14 distinct cell types and providing evidence of plaque tertiary lymphoid organs (PTLOs). The development of PTLOs was associated with the expression of lymphangiogenic chemokine genes and the adhesion molecule gene in fibroblast-like smooth muscle cells. PTLOs harbor abundant B cells with expanded and diversified B cell receptors, suggesting substantial immune involvement. We also observed that B cells may be exchanged between PTLOs and perivascular adipose tissues. The presence of PTLO-like structures correlates with cerebrovascular events, which may be mediated by PTLO-derived IgG antibodies enhancing macrophage functional activity. Our findings suggest the existence and characteristics of PTLOs in human atherosclerosis, elucidating their cellular functions and clinical implications and offering avenues for understanding, diagnosing and treating this condition.