1. C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis.
- Author
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Park, Inhye, Goddard, Michael E., Cole, Jennifer E., Zanin, Natacha, Lyytikäinen, Leo-Pekka, Lehtimäki, Terho, Andreakos, Evangelos, Feldmann, Marc, Udalova, Irina, Drozdov, Ignat, and Monaco, Claudia
- Subjects
MACROPHAGE colony-stimulating factor ,TOLL-like receptors ,MACROPHAGES ,CHOLESTEROL metabolism ,BONE marrow ,ATHEROSCLEROSIS - Abstract
Macrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via a LysM
Cre+ Clec4a2flox/DTR mouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease. The contribution of distinct subsets of macrophages to atherosclerosis is poorly understood. Here the authors describe a protective subset of vascular macrophages expressing the C-type lectin receptor CLEC4A2, which licenses monocytes to join the resident vascular macrophage pool and ensures vascular homeostasis. [ABSTRACT FROM AUTHOR]- Published
- 2022
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