腹主动脉瘤（AAA）严重危害人民健康，但其机制不清，且缺乏有效的药物治疗手段。干扰素调节因子5（IRF5）在调控巨噬细胞功能中有着重要作用，而巨噬细胞浸润在AAA的发病中起着重要作用，但IRF5是否以及如何参与AAA的发生发展仍未知。我们的预实验结果显示，AAA组织中，IRF5表达显著升高，且主要定位于巨噬细胞中；髓系特异性IRF5敲除可显著抑制弹力蛋白酶诱导的小鼠AAA形成。这些结果提示巨噬细胞IRF5参与AAA的发病。我们的细胞实验发现，巨噬细胞IRF5敲除调控迁移相关分子Pik3cg（PI3Kγ）mRNA，并可显著抑制巨噬细胞迁移。因此我们提出：AAA炎症环境中，被激活的巨噬细胞IRF5可通过上调PI3Kγ，促进巨噬细胞迁移并浸润于血管外膜，最终导致AAA的发生发展。为验证此假说，我们将利用多种组织特异性基因工程小鼠，体内及细胞水平验证巨噬细胞来源IRF5在AAA中的作用及机制。

Abdominal aortic aneurysm (AAA) is seriously threatening people's health, but the current mechanism is unclear and there is no effective means of drug control. Interferon regulatory factor 5 (IRF5) is essential in the regulation of macrophage function and macrophages play an important role in the pathogenesis of AAA. However, it is still unknown whether and how IRF5 participates in the development of AAA. Our preliminary data showed that the expression of IRF5 was significantly increased in AAA tissues and was mainly located in macrophages; myeloid-specific IRF5 knockdown significantly inhibited elastase-induced AAA formation in mice. These results suggest that macrophage-derived IRF5 participates in the development of AAA. Our cellullar data revealed that IRF5 knockdown regulated migration-related molecule Pik3cg (PI3Kγ) mRNA expression, and significantly inhibits macrophage migration. Therefore, we propose that in the AAA inflammatory environment, activated macrophage IRF5 can upregulate the transcription of Pik3cg mRNA, promote macrophage migration and infiltration in the adventitia, and eventually lead to the development of AAA. To test this hypothesis, we will use several tissue-specific lines of mice to verify the role and mechanisms of macrophage-derived IRF5 in AAA both in vitro and in vivo.