Cell Reports (Aug 2024)
Inherent preference for polyunsaturated fatty acids instigates ferroptosis of Treg cells that aggravates high-fat-diet-related colitis
- Junjie Yan,
- Yingying Zeng,
- Zerong Guan,
- Zhenhua Li,
- Shunchang Luo,
- Jie Niu,
- Junzhang Zhao,
- Haibiao Gong,
- Ting Huang,
- Zhongzhen Li,
- Anyi Deng,
- Qiong Wen,
- Jingyi Tan,
- Jun Jiang,
- Xiucong Bao,
- Sitao Li,
- Guodong Sun,
- Min Zhang,
- Min Zhi,
- Zhinan Yin,
- Wan-Yang Sun,
- Yi-Fang Li,
- Rong-Rong He,
- Guangchao Cao
Affiliations
- Junjie Yan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Yingying Zeng
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Department of Laboratory Medicine, Nanfang Hospital Baiyun Branch, Southern Medical University, Guangzhou 510420, China
- Zerong Guan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Zhenhua Li
- Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, China
- Shunchang Luo
- Department of Pediatrics, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Jie Niu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
- Junzhang Zhao
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510632, China
- Haibiao Gong
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China
- Ting Huang
- Department of Clinical Pathology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Zhongzhen Li
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China
- Anyi Deng
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Qiong Wen
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Jingyi Tan
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Jun Jiang
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China
- Xiucong Bao
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Sitao Li
- Department of Pediatrics, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guodong Sun
- Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People’s Hospital), Jinan University, Heyuan 517000, China
- Min Zhang
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510632, China
- Min Zhi
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510632, China; Corresponding author
- Zhinan Yin
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China; Corresponding author
- Wan-Yang Sun
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China; Corresponding author
- Yi-Fang Li
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China; Corresponding author
- Rong-Rong He
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China; Corresponding author
- Guangchao Cao
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University, Zhuhai 519000, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 8
p. 114636
Abstract
Summary: 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.
