Loss of SENP3 mediated the formation of nasal polyps in nasal mucosal inflammation by increasing alternative activated macrophage.

Feb 27, 2023

Experts: Ximing Bao,Bin Liu,Yongquan Jiang,Tingting Feng,Wanxin Cao,Jiali Shi,Yiming Jiang,Xiaorui Chen,Jie Yang,Jiping Li,Zheng Zhou

Small ubiquitin-like modifier (SUMO)-specific protease (SENP)3 is a protease molecule that responds to reactive oxygen species (ROS) with high sensitivity. However, the role of ROS and SENP3 in the formation of nasal polyps (NPs) remains unclear. This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis (CRS) by altering macrophage function, that is, the formation of NPs.
The alternative activation of macrophage (M2) was detected with CD68 CD206 in humans and CD206 in mice. The nasal mucosa of patients with CRS was tested using flow cytometry (CD68, CD80, and CD206) and triple-color immunofluorescence staining (CD68, CD206, and SENP3). The bone marrow-derived macrophages from SENP3 knockout and control mice were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative macrophage polarization in vitro. An animal model of allergic rhinitis was constructed using SENP3 knockout mice. CD206 was detected by immunofluorescence staining. The thickening of eosinophil-infiltrated mucosa was detected by Luna staining.
The number of CD68 CD206 M2 increased in the nasal mucosa of patients with CRS with NP (CRSwNP) compared with patients with CRS without NP (CRSsNP), but with no significant difference between the groups. SENP3 knockout increased the polarization of F4/80 CD206 M2. Meanwhile, the number of CD206 M2 significantly increased in the allergic rhinitis model constructed using SENP3 knockout mice and controls, with a more obvious proliferation of the nasal mucosa.
Downregulation of SENP3 promotes the formation of nasal polyps mediated by increasing alternative activated macrophage in nasal mucosal inflammation.

© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

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ABOUT THE EXPERTS

Ximing Bao,Bin Liu,Yongquan Jiang,Tingting Feng,Wanxin Cao,Jiali Shi,Yiming Jiang,Xiaorui Chen,Jie Yang,Jiping Li,Zheng Zhou

Ximing Bao

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Institutes of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Bin Liu

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Yongquan Jiang

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Tingting Feng

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Wanxin Cao

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Jiali Shi

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Yiming Jiang

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Xiaorui Chen

Anesthesia Department of Shanghai International Medical Center, Shanghai, China.

Jie Yang

Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Institutes of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Jiping Li

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Zheng Zhou

Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Institutes of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.