IL-3/CD123轴调控B淋巴细胞介导的免疫炎症反应促进胸主动脉瘤/夹层形成的机制研究

Thoracic aortic aneurysm / dissection (TAAD) is a kind of dangerous and fatal vascular disease. The infiltration of inflammatory cells in blood vessels is an important factor in the formation of TAAD. Our preliminary studies suggested that B lymphocytes were significantly increased in peripheral blood of TAAD patients and vascular tissue and peripheral blood of TAAD mice induced by β-aminopropionitrile (BAPN). IL-3, a pro-TAAD inflammatory factor, could regulate the proliferation and survival of B lymphocytes by binding to its receptor CD123. However, the role and mechanism of B lymphocytes in the occurrence and development of TAAD remain unclear, and whether IL-3 can promote the formation of TAAD by regulating the function of B lymphocytes remains to be verified. Therefore, we propose a scientific hypothesis that "the IL-3/CD123 axis regulates the B lymphocyte mediated inflammatory response and promotes the formation of TAAD". In this study, CD20 neutralizing antibody was used to treat the mice to clarify the effect of B lymphocytes on the formation of TAAD. The mice were treated with IL-3 recombinant protein and CD123 neutralizing antibody, and combined with cell test in vitro, to clarify how the IL-3/CD123 axis regulates the function of B lymphocytes promoting the formation of TAAD. This study will provide a supplement of theoretical for the study of pathogenesis of TAAD, and a new way of the treatment.

胸主动脉瘤/夹层（TAAD）是一类凶险、致死率高的血管疾病，炎症细胞在血管中浸润是介导TAAD形成的重要因素。前期研究发现，B淋巴细胞在TAAD患者外周血以及赖氨酰氧化酶抑制剂诱导的TAAD模型小鼠的外周血和血管组织中显著升高。促TAAD形成的炎症因子IL-3可通过受体CD123调控B淋巴细胞增殖和存活。但B淋巴细胞在TAAD发生发展过程中的作用及机制尚不清楚，IL-3是否通过调控B淋巴细胞功能促进TAAD形成尚需验证。据此我们提出科学假设“IL-3/CD123轴调控B淋巴细胞相关炎症反应促进TAAD形成”。本课题将利用CD20中和抗体处理模型小鼠阐明B淋巴细胞对TAAD形成的影响，使用IL-3重组蛋白、CD123中和抗体处理模型小鼠，结合体外细胞实验，拟明确IL-3/CD123轴如何调控B淋巴细胞功能影响TAAD形成的分子机制。本课题将为TAAD的机制研究提供理论补充，为治疗提供新思路。

胸主动脉瘤/夹层（TAAD）是一类凶险、致死率高的血管疾病，炎症细胞在主动脉中浸润是介导TAAD形成的重要因素。近年来多项针对TAAD的单细胞测序研究提示TAAD血管组织中B淋巴细胞浸润增加。但B淋巴细胞在TAAD中的作用及机制尚不完全明确。本项目成功构建了β-氨基丙腈（BAPN）诱导的TAAD小鼠模型，明确了B淋巴细胞在TAAD血管组织及外周血中的表达情况。我们通过anti-CD20中和抗体在TAAD诱导过程中敲除B淋巴细胞，探索B淋巴细胞对TAAD的作用和机制。敲除B淋巴细胞能一定程度上减少主动脉平滑肌的丢失，但对成瘤率和破裂率无显著影响。另外还可诱导外周血中CD4+T细胞比例升高、CD8+T细胞比例降低，而在脾脏中则是CD4+T细胞比例降低而CD8+T细胞比例升高，提示在TAAD过程中，B淋巴细胞对T淋巴细胞发挥重要调控作用。本课题深入探讨了B淋巴细胞在TAAD中的作用及机制，为TAAD的机制研究提供新的实验依据和理论补充。