动脉粥样硬化是以内膜病变为主的一种血管慢性炎症病变，研究者常常聚焦血管内膜而忽略对血管外膜的研究。我们研究发现老龄的Apoe-/-小鼠腹主动脉外膜形成免疫细胞集聚的三级淋巴组织，但其在动脉粥样硬化发病过程中的作用尚不明确。我们前期研究显示，伴随血管外膜免疫细胞的集聚，出现神经纤维在外膜的大量浸润，且二者之间存在紧密的空间联系，而血管中膜平滑肌细胞特异性缺失LTbR致使外膜免疫细胞和神经浸润减少，并伴随内膜斑块的增大。据此，我们提出LTbR信号通路通过介导外膜神经纤维与免疫细胞之间的“对话”抑制内膜斑块的假说，通过基因敲除小鼠，并采用神经阻断术、质谱流式、组织化学染色术及基因组测序等技术，研究动脉外膜神经分布图谱，神经-免疫互作及其抑制内膜动脉粥样硬化斑块形成的机理，阐明LTbR信号通路通过介导外膜神经纤维浸润并与免疫细胞“对话”调控血管区域免疫的机制，为临床心血管疾病的诊疗提供新的思路。

Atherosclerosis is considered to be a chronic inflammation of blood vessels with intima lesions. Researchers often focus on the intima of blood vessels rather than on the adventitia. We have found that the adventitia of the abdominal aorta of the aged Apoe-/- mice forms the artery tertiary lymphoid organs with immune cell aggregation, but its role in the pathogenesis of atherosclerosis is still unclear. Our previous studies have shown that with the accumulation of adventitia immune cells, there is a large number of infiltration of nerve fibers in adventitia, and there is a close spatial relationship between them. The tissue specific deletion of LTbR in vascular smooth muscle cells reduces the infiltration of adventitia immune cells and nerves, and however the increase of intimal plaque. Accordingly, we propose the hypothesis that LTbR signaling pathway inhibits the formation of intimal plaque by mediating "dialogue" between adventitial nerve fibers and immune cells. By using gene knockout mouse model, we studied the distribution pattern of adventitia nerve and neuro-immune interaction by means of nerve blockade, CytoF flow cytometry, histochemical staining and genome sequencing. Our study will clarify the mechanism of LTbR signaling pathway regulating the immune inflammation reaction in vascular region through mediating the dialogue between adventitia nerve fibers and immune cells, and provide new ideas and therapeutic targets for clinical diagnosis and treatment of cardiovascular diseases.