STAT1 mediates the pro-inflammatory role of GBP5 in colitis
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 decr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07843-0 |
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| author | Yichen Li Wenxia Wang Ruixin Zhu Xinyue Zhu Mingwei Sun Yanlan Huang Wanning Chen Sheng Gao Na Jiao Xutao Lin Jia Ke Tao Xu Linlin Hou Ping Lan Lixin Zhu |
| author_facet | Yichen Li Wenxia Wang Ruixin Zhu Xinyue Zhu Mingwei Sun Yanlan Huang Wanning Chen Sheng Gao Na Jiao Xutao Lin Jia Ke Tao Xu Linlin Hou Ping Lan Lixin Zhu |
| author_sort | Yichen Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c9562da4c3914cfdb85535ee57c1a1f2 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c9562da4c3914cfdb85535ee57c1a1f22025-08-20T01:57:27ZengNature PortfolioCommunications Biology2399-36422025-03-018111310.1038/s42003-025-07843-0STAT1 mediates the pro-inflammatory role of GBP5 in colitisYichen Li0Wenxia Wang1Ruixin Zhu2Xinyue Zhu3Mingwei Sun4Yanlan Huang5Wanning Chen6Sheng Gao7Na Jiao8Xutao Lin9Jia Ke10Tao Xu11Linlin Hou12Ping Lan13Lixin Zhu14Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen UniversityThe Shanghai Tenth People’s Hospital, School of Life Sciences and Technology, Tongji UniversityThe Shanghai Tenth People’s Hospital, School of Life Sciences and Technology, Tongji UniversityBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)School of Medicine, Shenzhen Campus of Sun Yat-sen UniversityThe Shanghai Tenth People’s Hospital, School of Life Sciences and Technology, Tongji UniversityThe Shanghai Tenth People’s Hospital, School of Life Sciences and Technology, Tongji UniversityState Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan UniversityGuangdong 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 UniversityGuangdong 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 UniversityDepartment of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen UniversitySchool of Medicine, Shenzhen Campus of Sun Yat-sen UniversityGuangdong 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 UniversityGuangdong 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 UniversityAbstract 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.https://doi.org/10.1038/s42003-025-07843-0 |
| spellingShingle | Yichen Li Wenxia Wang Ruixin Zhu Xinyue Zhu Mingwei Sun Yanlan Huang Wanning Chen Sheng Gao Na Jiao Xutao Lin Jia Ke Tao Xu Linlin Hou Ping Lan Lixin Zhu STAT1 mediates the pro-inflammatory role of GBP5 in colitis Communications Biology |
| title | STAT1 mediates the pro-inflammatory role of GBP5 in colitis |
| title_full | STAT1 mediates the pro-inflammatory role of GBP5 in colitis |
| title_fullStr | STAT1 mediates the pro-inflammatory role of GBP5 in colitis |
| title_full_unstemmed | STAT1 mediates the pro-inflammatory role of GBP5 in colitis |
| title_short | STAT1 mediates the pro-inflammatory role of GBP5 in colitis |
| title_sort | stat1 mediates the pro inflammatory role of gbp5 in colitis |
| url | https://doi.org/10.1038/s42003-025-07843-0 |
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