Xcr1+ type 1 conventional dendritic cells are essential mediators for atherosclerosis progression

作者：Tianhan Li, Liaoxun Lu, Juanjuan Qiu, Xin Dong, Le Yang, Kan He, Yanrong Gu, Binhui Zhou, Tingting Jia, Toby Lawrence, Marie Malissen, Guixue Wang, Rong Huang, Hui Wang, Bernard Malissen, Yinming Liang, Lichen Zhang · 发表于：eLife · 年份：2025 · DOI：10.7554/elife.107742 · 被引用次数：3 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Cell Adhesion Molecules Research、T-cell and B-cell Immunology

Atherosclerosis is characterized by lipid accumulation within plaques, leading to foam cell formation and an inflammatory response within the aortic lesions. Lipid disorders have been extensively investigated, however, the cellular and molecular mechanisms that trigger the inflammatory response in atherosclerotic plaques remain far from being fully understood. Xcr1 + cDC1 cells are newly identified antigen-presenting cells in activating immune cells. However, the role of cDC1 cells in atherosclerosis development remains highly controversial. We first confirmed the presence of cDC1 within human atherosclerotic plaques and discovered a significant association between the increasing cDC1 numbers and atherosclerosis progression in mice. Subsequently, we established Xcr1 Cre-Gfp Rosa26 LSL-DTA Apoe –/– mice, a novel and complex genetic model, in which cDC1 was constitutively depleted in vivo during atherosclerosis development. Intriguingly, we observed a notable reduction in atherosclerotic lesions in hyperlipidemic mice, alongside suppressed T cell activation of both CD4 + and CD8 + subsets in the aortic plaques. Notably, aortic macrophages and serum lipid levels were not significantly changed in the cDC1-depleted mice. Single-cell RNA sequencing revealed heterogeneity of Xcr1 + cDC1 cells across the aorta and lymphoid organs under hyperlipidemic conditions. As Xcr1 is the sole receptor for Xcl1, we next explored to target Xcr1 + cDC1 cells via Xcl1 by establishing Xcl1 –/– Apoe ...