Deficiency of IL-7R attenuates abdominal aortic aneurysms in mice by inhibiting macrophage polarization towards M1 phenotype through the NF-κB pathway

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 31; no. 1; pp. 138 - 17
• Main Authors: Xu, Shengnan, Han, Xueyu, Yu, Yi, Qu, Chuan, Yang, Bo, Shen, Bo, Liu, Xin
• Format: Journal Article
• Language: English
• Published: England BioMed Central 16.04.2025; BMC
• Subjects: Abdominal aortic aneurysm; Animals; Aortic Aneurysm, Abdominal - etiology; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - pathology; Disease Models, Animal; IL-7/IL-7R; M1 macrophage polarization; Macrophage Activation; Macrophages; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - metabolism; NF-κB pathway; Phenotype; RAW 264.7 Cells; Receptors, Interleukin-7 - deficiency; Receptors, Interleukin-7 - genetics; Receptors, Interleukin-7 - metabolism; Signal Transduction; IL-7/IL-7R; Macrophages; M1 macrophage polarization; Abdominal aortic aneurysm; NF-κB pathway
• ISSN: 1528-3658; 1076-1551; 1528-3658
• DOI: 10.1186/s10020-025-01209-2

Abdominal aortic aneurysm (AAA) is a common degenerative disease of the abdominal aorta, which can result in extremely high mortality owing to the rupture of the abdominal aorta. The activation of IL-7R has been shown to modulate the inflammatory responses, which play an important role in the progression of AAAs. However, the mechanism of IL-7/IL-7R axis in AAAs is still unclear. This study aims to investigate the effects of IL-7R on AAAs and the underlying mechanisms involved. Wild-type C57BL/6 and IL-7R knockout mice were used as experimental subjects. ELISA analysis, histological staining, western blotting and qPCR were performed to explore effects of IL-7R deficiency in the formation and development of elastase-induced AAAs. Transwell, CCK8, and immunofluorescence assays detected the migration and polarization of RAW264.7 macrophages in vitro. We demonstrated that IL-7R was elevated in mice with AAAs. Blocking IL-7R can inhibit the formation of AAAs and reduce aortic dilatation, elastic layer degradation, and inflammatory cell infiltration. Knockout of IL-7R suppressed the migration, infiltration and M1 polarization of macrophages. Moreover, inhibition of the NF-κB signaling pathway by BAY 11-7082 attenuated the macrophage-mediated inflammatory responses caused by IL-7R overexpression. In short, this study showed that IL-7R promotes the infiltration and migration of macrophages by regulating M1 macrophage polarization, possibly in part via activation of the NF-κB pathway, which may be associated with the development of AAAs.