2. Academic Validation
  3. Vps34 sustains Treg cell survival and function via regulating intracellular redox homeostasis

Vps34 sustains Treg cell survival and function via regulating intracellular redox homeostasis

  • Cell Death Differ. 2024 Aug 8. doi: 10.1038/s41418-024-01353-y.
Peiran Feng # 1 2 3,  Quanli Yang # 1,  Liang Luo # 1 3,  Zerong Guan # 1 3,  Jiamin Fu 1 3,  Mingyue Zhao 1 3,  Wanqing Meng 1 3,  Shuo Wan 4,  Junming He 5,  Zhizhong Li 2,  Guang Wang 4,  Guodong Sun 2,  Zhongjun Dong 6,  Meixiang Yang 7 8 9 10
Affiliations

Affiliations

  • 1 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, China.
  • 2 Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China.
  • 3 State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, China.
  • 4 International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China.
  • 5 The First Affiliated Hospital of Anhui Medical University and Institute for Clinical Immunology, Anhui Medical University, Hefei, Anhui, China.
  • 6 The First Affiliated Hospital of Anhui Medical University and Institute for Clinical Immunology, Anhui Medical University, Hefei, Anhui, China. dongzj@mail.tsinghua.edu.cn.
  • 7 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, China. mxyang@jnu.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, China. mxyang@jnu.edu.cn.
  • 9 State Key Laboratory of Bioactive Molecules and Druggability Assessment, The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, China. mxyang@jnu.edu.cn.
  • 10 Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control (Jinan University). Guangzhou Key Laboratory for Germ-Free Animals and Microbiota Application. Institute of Laboratory Animal Science, School of Medicine, Jinan University, Guangzhou, China. mxyang@jnu.edu.cn.
  • # Contributed equally.
PMID: 39117783 DOI: 10.1038/s41418-024-01353-y
Abstract

The survival and suppressive function of regulatory T (Treg) cells rely on various intracellular metabolic and physiological processes. Our study demonstrates that Vps34 plays a critical role in maintaining Treg cell homeostasis and function by regulating cellular metabolic activities. Disruption of Vps34 in Treg cells leads to spontaneous fatal systemic autoimmune disorder and multi-tissue inflammatory damage, accompanied by a reduction in the number of Treg cells, particularly eTreg cells with highly immunosuppressive activity. Mechanistically, the poor survival of Vps34-deficient Treg cells is attributed to impaired endocytosis, intracellular vesicular trafficking and autophagosome formation, which further results in enhanced mitochondrial respiration and excessive ROS production. Removal of excessive ROS can effectively rescue the death of Vps34-deficient Treg cells. Functionally, acute deletion of Vps34 within established Treg cells enhances anti-tumor immunity in a malignant melanoma model by boosting T-cell-mediated anti-tumor activity. Overall, our results underscore the pivotal role played by Vps34 in orchestrating Treg cell homeostasis and function towards establishing immune homeostasis and tolerance.

Figures
Products
Inhibitors & Agonists