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Updated: Sep 8, 2025
07:17
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
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Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1
Hongrui Xiang1, Yuexiao Tao1, Zhenyan Jiang1
1Shanghai Institute of Immunology, Department of Immunology and Microbiology, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Cell Reports
|June 15, 2022
Summary
Regulatory T (Treg) cells control immune suppression via mTORC1. Vps33B deficiency disrupts Treg function by impairing lysosome fusion, boosting antitumor immunity.
Area of Science:
- Immunology
- Cell Biology
- Metabolism
Background:
- Regulatory T (Treg) cell function is critical for immune suppression.
- The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates Treg cell activity.
- The precise regulation and negative control of Treg cell suppressive function remain incompletely understood.
Purpose of the Study:
- To investigate the role of vacuolar protein sorting 33B (Vps33B) in Treg cell function and homeostasis.
- To elucidate the molecular mechanisms by which Vps33B regulates Treg cell suppressive activity.
- To determine the impact of Vps33B deficiency on antitumor immunity.
Main Methods:
- Treg-specific depletion of Vps33B in a mouse model.
- Analysis of Treg cell suppressive function and phenotype.
- Investigation of endolysosomal trafficking and mTORC1 activation.
- Assessment of T cell homeostasis and antitumor immune responses.
Main Results:
- Treg-specific Vps33B depletion impairs Treg cell suppressive function and promotes an effector phenotype.
- Vps33B deficiency leads to defective endolysosome fusion and accumulation of the lysosomal nutrient-sensing complex (LYNUS).
- Accumulated LYNUS results in elevated mTORC1 activation, hyper-glycolytic metabolism, disturbed T cell homeostasis, and enhanced antitumor immunity.
Conclusions:
- Vps33B is essential for maintaining Treg cell suppressive function by regulating endolysosomal homeostasis.
- Vps33B restricts mTORC1 activation and metabolism in Treg cells.
- Vps33B acts as a negative regulator of mTORC1 signaling in Treg cells, impacting immune suppression and antitumor responses.
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