Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice

Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α+ and CD103+ DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr-/-)-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α+ and CD103+ antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.

动脉粥样硬化（Atherosclerosis）是心肌梗死（myocardial infarction）、脑卒中（stroke）等心血管事件的主要潜在病因，其发生发展可能受免疫细胞调控。树突状细胞（Dendritic cells, DCs）通过向T细胞呈递抗原并分泌多种细胞因子，连接固有免疫与适应性免疫应答。现已可区分出多类DC亚群，此类亚群依赖特定转录通路完成发育。碱性亮氨酸拉链转录因子ATF样3（Batf3）是经典CD8α阳性与CD103阳性DC发育所必需的转录因子。本研究将Batf3缺陷小鼠与易患动脉粥样硬化的低密度脂蛋白受体（low density lipoprotein receptor）缺陷（Ldlr-/-）小鼠杂交，旨在进一步探究Batf3依赖的CD8α阳性、CD103阳性抗原呈递细胞（antigen-presenting cells）在动脉粥样硬化中的作用。研究结果显示，Batf3缺陷仅对脾脏免疫应答产生轻微影响，既未改变高脂饮食喂养的低密度脂蛋白受体缺陷（Ldlr-/-）小鼠的主动脉及主动脉根部动脉粥样硬化斑块形成情况，亦未影响其斑块表型。综上，本研究证实Batf3依赖的抗原呈递细胞在动脉粥样硬化进程中未发挥显著作用。