2. Academic Validation
  3. STAT1 mediates the pro-inflammatory role of GBP5 in colitis

STAT1 mediates the pro-inflammatory role of GBP5 in colitis

  • Commun Biol. 2025 Mar 7;8(1):385. doi: 10.1038/s42003-025-07843-0.
Yichen Li # 1 2 3,  Wenxia Wang # 1 3 4,  Ruixin Zhu 5,  Xinyue Zhu 6,  Mingwei Sun 7,  Yanlan Huang 8,  Wanning Chen 6,  Sheng Gao 6,  Na Jiao 9,  Xutao Lin 3,  Jia Ke 3,  Tao Xu 1 2,  Linlin Hou 10,  Ping Lan 11,  Lixin Zhu 12 13
Affiliations

Affiliations

  • 1 Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 2 Medical College, Jiaying University, Meizhou, China.
  • 3 Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases; Biomedical Innovation Center; Department of General Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 4 Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 5 The Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. rxzhu@tongji.edu.cn.
  • 6 The Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 7 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.
  • 8 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • 9 State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China.
  • 10 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China. houllin3@mail.sysu.edu.cn.
  • 11 Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases; Biomedical Innovation Center; Department of General Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. lanping@mail.sysu.edu.cn.
  • 12 Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases; Biomedical Innovation Center; Department of General Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 111974335@imu.edu.cn.
  • 13 Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia University, Hohhot, China. 111974335@imu.edu.cn.
  • # Contributed equally.
PMID: 40055493 DOI: 10.1038/s42003-025-07843-0
Abstract

Previous studies establish guanylate binding protein 5 (GBP5) as a driver in the development of inflammatory bowel diseases (IBDs). Here, we aim to elucidate the mechanism underlying the pro-inflammatory role of GBP5. We observe that loss of Gbp5 causes reduced colonic inflammation and decreased numbers of innate lymphoid cells (ILCs) in colitis mice. The transcriptional alterations observed in GBP5-deficient THP-1 cells mirrored those triggered by STAT1 activation, leading to the findings that GBP5 is essential for the stimulated expression of STAT1 and its downstream effectors, including cytokines that drive the expansion of ILCs. Remarkably, over-expression of STAT1 reverses the reduced cytokine expression caused by GBP5 deficiency. While GBP5 does not directly drive gene transcription, it binds with STAT1 and facilitates its nuclear translocation, thereby enhancing the expression of STAT1 itself and its downstream effectors. Overall, GBP5 plays a pro-inflammatory role in IBD by enhancing the activity and expression of STAT1.

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