Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice

Zhao-yang Wang, Jie Cheng, Ying Wang, Hai-tao Yuan, Shao-jie Bi, Shuang-xi Wang, Ya-min Hou, Xu Zhang, Bo-han Xu, Ze-ying Wang, Yun Zhang (), Wen-jian Jiang (), Yu-guo Chen () and Ming-xiang Zhang ()
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Zhao-yang Wang: Qilu Hospital of Shandong University
Jie Cheng: Qilu Hospital of Shandong University
Ying Wang: Qilu Hospital of Shandong University
Hai-tao Yuan: Shandong Provincial Hospital Affiliated to Shandong First Medical University
Shao-jie Bi: Shandong University
Shuang-xi Wang: Qilu Hospital of Shandong University
Ya-min Hou: Qilu Hospital of Shandong University
Xu Zhang: Qilu Hospital of Shandong University
Bo-han Xu: Qilu Hospital of Shandong University
Ze-ying Wang: Qilu Hospital of Shandong University
Yun Zhang: Qilu Hospital of Shandong University
Wen-jian Jiang: Capital Medical University
Yu-guo Chen: Shandong University
Ming-xiang Zhang: Qilu Hospital of Shandong University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

Date: 2024
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DOI: 10.1038/s41467-024-51030-4

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