Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2025; 31(27): 109239
Published online Jul 21, 2025. doi: 10.3748/wjg.v31.i27.109239
Translocator protein facilitates neutrophil-mediated mucosal inflammation in inflammatory bowel diseases
Qiong He, Xiao-Han Wu, Dong-Lang Jiang, Ri-Tian Lin, Fang Xie, Yi-Hui Guan, Ai-Hua Fei
Qiong He, Ai-Hua Fei, Department of General Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Xiao-Han Wu, Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Dong-Lang Jiang, Fang Xie, Yi-Hui Guan, Department of Nuclear Medicine, PET Center, Huashan Hospital, Fudan University, Shanghai 200040, China
Ri-Tian Lin, Department of Gastroenterology, Shanghai East Hospital, Tongji University of School Medicine, Shanghai 200120, China
Co-first authors: Qiong He and Xiao-Han Wu.
Co-corresponding authors: Yi-Hui Guan and Ai-Hua Fei.
Author contributions: He Q and Wu XH performed the experiments, analyzed the samples, and interpreted the results; He Q, Wu XH, and Jiang DL collected data and performed the analyses; He Q and Jiang DL prepared the manuscript; Xie F interpreted the results and revised the manuscript; Guan YH and Fei AH conceived and designed the study; all authors have reviewed and approved the manuscript before submission.
Supported by National Natural Science Foundation of China, No. 82300604; and Science and Technology Innovation Action Plan Star Project Application Guide/Star Project Incubation (Yangfan Special Program) of Shanghai, No. 24YF2727600.
Institutional review board statement: The study was approved by the Ethics Committee of Shanghai East Hospital of Tongji University (No. 2024YS-232). Written informed consent was obtained from all participants prior to their inclusion in the study.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Tongji University, Shanghai (No. TJBB05424103).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ai-Hua Fei, Chief Physician, Department of General Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. feiaihua@xinhuamed.com.cn
Received: May 6, 2025
Revised: May 28, 2025
Accepted: June 16, 2025
Published online: July 21, 2025
Processing time: 78 Days and 7.8 Hours
Abstract
BACKGROUND

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact. The exact etiology of this condition remains unclear. Neutrophils play a critical role in IBD pathogenesis. Translocator protein (TSPO), a mitochondrial protein linked to immune responses, has demonstrated potential as an inflammatory marker. However, its role in IBD remains underexplored.

AIM

To investigate the role of TSPO in IBD pathogenesis, particularly in neutrophils.

METHODS

Bioinformatics analyses of Gene Expression Omnibus datasets (GE75214, GSE94648, GSE156776) assessed TSPO expression in IBD patients. TSPO expression was evaluated in human IBD samples, neutrophiles and a chronic colitis mouse model. Neutrophil function was examined in 18 samples using reactive oxygen species (ROS) production and neutrophil extracellular trap (NET) formation assays. Positron emission tomography-computed tomography (PET-CT) imaging and histology from 12 mice revealed TSPO expression in colitis. PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.

RESULTS

Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD, especially in neutrophils. This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining, which showed a significant upregulation of TSPO in active IBD. Neutrophils from patients with UC and CD exhibited higher TSPO expression, which correlated with increased ROS production and NET formation. In a mouse model of dextran sodium sulfate-induced chronic colitis, TSPO was upregulated in the colonic neutrophils and brain tissues, indicating its systemic involvement. PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions, particularly in the microglia, highlighting neuroinflammation.

CONCLUSION

TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation. Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.

Keywords: Inflammatory bowel disease; Ulcerative colitis; Crohn's disease; Translocator protein; Expression; Neutrophil; Intestinal inflammation; Neuroinflammation; Positron emission tomography-computed tomography; Gut-brain axis

Core Tip: This research recognizes translocator protein (TSPO) as a novel biomarker and promising therapeutic target for inflammatory bowel diseases (IBD). Elevated TSPO expression was observed in neutrophils of IBD patients, along with increased reactive oxygen species production and neutrophil extracellular trap formation. Additionally, upregulated TSPO in both the inflamed colon and brain tissue suggests its contributions to autoimmune inflammation and neuroinflammation. These findings recommend TSPO as a potential target for IBD treatment, highlighting its role in both intestinal and neurological inflammatory processes.