Bellini Rossella, Moregola Annalisa, Nour Jasmine, Rombouts Yoann, Neyrolles Olivier, Uboldi Patrizia, Bonacina Fabrizia, Norata Giuseppe Danilo
Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France.
Atheroscler Plus. 2022 Dec 17;51:8-12. doi: 10.1016/j.athplu.2022.12.001. eCollection 2023 Mar.
Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immunoreceptor 2) is a C-type lectin receptor, mainly expressed by CD8α DCs, able to modulate T cell immunity. However, whether this DC subset could play a role in the atherogenesis is still poorly understood. Thus, the aim of this study is to investigate whether the absence of Clec4a4 could affect atherosclerosis-related immune response and atherosclerosis itself.
and mice were fed a standard diet or cholesterol-enriched diet for 12 weeks. Subsequently, the profile of circulating and lymph nodes-resident immune cells was investigated together with the analysis of plasma lipid levels and atherosclerotic plaque extension in the aorta.
Here, we show that expression is downregulated under hypercholesterolemia and its deficiency in mice results in the reduction of atherosclerotic plaque formation, together with altered lipid metabolism and impaired myeloid immune cell distribution.
Our findings suggest a pro-atherosclerotic role of Clec4a4 in experimental atherosclerosis.
动脉粥样硬化的发生源于脂质代谢改变和免疫反应受损。新出现的证据表明，树突状细胞（DCs）参与动脉粥样硬化相关的免疫反应，但其影响鲜有描述。Clec4a4或DCIR2（树突状细胞免疫受体2）是一种C型凝集素受体，主要由CD8α DCs表达，能够调节T细胞免疫。然而，这个DC亚群是否在动脉粥样硬化发生中发挥作用仍知之甚少。因此，本研究的目的是探究Clec4a4缺失是否会影响动脉粥样硬化相关的免疫反应以及动脉粥样硬化本身。
将野生型小鼠和Clec4a4基因敲除小鼠喂食标准饮食或富含胆固醇的饮食12周。随后，研究循环和淋巴结驻留免疫细胞的情况，并分析血浆脂质水平和主动脉粥样硬化斑块的扩展情况。
在此，我们表明在高胆固醇血症情况下Clec4a4表达下调，并且Clec4a4基因敲除小鼠中其缺乏导致动脉粥样硬化斑块形成减少，同时脂质代谢改变和髓样免疫细胞分布受损。
我们的研究结果表明Clec4a4在实验性动脉粥样硬化中具有促动脉粥样硬化作用。
