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

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

  • Mol Med. 2025 Apr 16;31(1):138. doi: 10.1186/s10020-025-01209-2.
Shengnan Xu # 1 2 3,  Xueyu Han # 1 2 3,  Yi Yu 1 2 3,  Chuan Qu 1 2 3,  Bo Yang 4 5 6,  Bo Shen 7 8 9,  Xin Liu 10 11 12
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, P.R. China.
  • 2 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, P.R. China.
  • 3 Hubei Key Laboratory of Cardiology, Wuhan, 430060, P.R. China.
  • 4 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, P.R. China. yybb112@whu.edu.cn.
  • 5 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, P.R. China. yybb112@whu.edu.cn.
  • 6 Hubei Key Laboratory of Cardiology, Wuhan, 430060, P.R. China. yybb112@whu.edu.cn.
  • 7 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, P.R. China. shenbowhdx@126.com.
  • 8 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, P.R. China. shenbowhdx@126.com.
  • 9 Hubei Key Laboratory of Cardiology, Wuhan, 430060, P.R. China. shenbowhdx@126.com.
  • 10 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, P.R. China. RM003805@whu.edu.cn.
  • 11 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, P.R. China. RM003805@whu.edu.cn.
  • 12 Hubei Key Laboratory of Cardiology, Wuhan, 430060, P.R. China. RM003805@whu.edu.cn.
  • # Contributed equally.
PMID: 40240976 DOI: 10.1186/s10020-025-01209-2
Abstract

Background: 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.

Aims: This study aims to investigate the effects of IL-7R on AAAs and the underlying mechanisms involved.

Methods: 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.

Result: 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.

Conclusion: 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.

Keywords

Abdominal aortic aneurysm; IL-7/IL-7R; M1 macrophage polarization; Macrophages; NF-κB pathway.

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