STAT1 mediates the pro-inflammatory role of GBP5 in colitis
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.
Authors
- Ping Lan (ORCID: https://orcid.org/0000-0002-8901-8498)
- Xinyue Zhu (ORCID: https://orcid.org/0009-0009-4168-6196)
- Linlin Hou (ORCID: https://orcid.org/0000-0002-9235-1582)
- Xutao Lin (ORCID: https://orcid.org/0000-0002-7110-3459)
- Yichao Huang (ORCID: https://orcid.org/0000-0001-8127-3657)
- Lixin Zhu (ORCID: https://orcid.org/0000-0001-7904-1769)
- Wanning Chen (ORCID: https://orcid.org/0000-0003-0167-9257)
- Mingwei Sun (ORCID: https://orcid.org/0000-0002-2433-3016)
- Na Jiao (ORCID: https://orcid.org/0000-0003-3976-6313)
- Yichen Li (ORCID: https://orcid.org/0000-0002-4326-6285)
- Wenxia Wang (ORCID: https://orcid.org/0000-0001-9861-418X)
- Ruixin Zhu (ORCID: https://orcid.org/0000-0002-5070-6453)
- Sheng Gao (ORCID: https://orcid.org/0000-0002-3726-3416)
- Tao Xu (ORCID: https://orcid.org/0000-0003-3084-4645)
- Ke Jia (ORCID: https://orcid.org/0009-0005-5498-8952)
Institutions
- Tongji University (CN)
- Sun Yat-sen University (CN)
- Jiaying University (CN)
- Fudan University (CN)
- Inner Mongolia University (CN)
- Sixth Affiliated Hospital of Sun Yat-sen University (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Shanghai Tenth People's Hospital (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s42003-025-07843-0
- Citations
- 3
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 2.39