| First Author | Wang Y | Year | 2024 |
| Journal | JCI Insight | Volume | 9 |
| Issue | 3 | PubMed ID | 38175709 |
| Mgi Jnum | J:360482 | Mgi Id | MGI:7797626 |
| Doi | 10.1172/jci.insight.171488 | Citation | Wang Y, et al. (2024) IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation. JCI Insight 9(3) |
| abstractText | Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase gamma (PI3Kgamma, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kgamma expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kgamma is essential for AAA formation. |
