Inherent preference for polyunsaturated fatty acids instigates ferroptosis of Treg cells that aggravates high-fat-diet-related colitis
Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.
Authors
- Guodong Sun (ORCID: https://orcid.org/0000-0001-5336-368X)
- Wan‐Yang Sun (ORCID: https://orcid.org/0000-0002-4439-967X)
- Zerong Guan
- Anyi Deng
- Junjie Yan (ORCID: https://orcid.org/0000-0001-8890-225X)
- Min Zhi (ORCID: https://orcid.org/0000-0001-8178-5572)
- Jun Jiang (ORCID: https://orcid.org/0000-0002-6342-165X)
- Ting Huang (ORCID: https://orcid.org/0000-0002-8755-043X)
- Sitao Li (ORCID: https://orcid.org/0000-0002-4035-8635)
- Guangchao Cao (ORCID: https://orcid.org/0000-0003-2069-3396)
- Zhinan Yin (ORCID: https://orcid.org/0000-0001-6524-8777)
- Qiong Wen (ORCID: https://orcid.org/0000-0002-0517-8460)
- Xiucong Bao (ORCID: https://orcid.org/0000-0001-8069-8194)
- Yingying Zeng (ORCID: https://orcid.org/0000-0003-1728-820X)
- Zhenhua Li (ORCID: https://orcid.org/0000-0001-6188-9454)
- M. Zhang (ORCID: https://orcid.org/0000-0001-8659-5727)
- Yi-Fang Li
- Junzhang Zhao
- Rongrong He (ORCID: https://orcid.org/0000-0002-0664-7708)
- Zhongzhen Li (ORCID: https://orcid.org/0000-0002-8858-0550)
- Jie Niu
- Shunchang Luo
- Haibiao Gong
- Jingyi Tan (ORCID: https://orcid.org/0009-0001-8597-6998)
Institutions
- Guangzhou University of Chinese Medicine (CN)
- Sun Yat-sen University (CN)
- Jinan University (CN)
- Sixth Affiliated Hospital of Sun Yat-sen University (CN)
- Zhuhai People's Hospital (CN)
- First Affiliated Hospital of Jinan University (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-08-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114636
- Citations
- 35
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 14.66
Funders
- Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease
- Natural Science Foundation of Guangzhou City
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Food and Health Bureau
- Guangdong Science and Technology Department
- National Aerospace Science Foundation of China
- Novo Nordisk Foundation Center for Basic Metabolic Research
- Higher Education Discipline Innovation Project
- Guangzhou Municipal Science and Technology Bureau
- Guangdong Province Introduction of Innovative R&D Team
- Health and Medical Research Fund
- National Key Research and Development Program of China
- Project 211
- Basic and Applied Basic Research Foundation of Guangdong Province