| Autor: |
Hongrui Xiang, Yuexiao Tao, Zhenyan Jiang, Xian Huang, Huizi Wang, Wei Cao, Jia Li, Rui Ding, Mingyi Shen, Ru Feng, Linsen Li, Chenyang Guan, Jiamin Liu, Jun Ni, Lei Chen, Zhengting Wang, Youqiong Ye, Qing Zhong, Junling Liu, Qiang Zou, Xuefeng Wu |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 39, Iss 11, Pp 110943- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2022.110943 |
| Popis: |
Summary: The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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