Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development
Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development
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调节性 T 细胞中缺乏磷脂酰肌醇 3-激酶 VPS34 会导致致命的淋巴增殖性疾病，但不会影响其发育
DOI：
10.1101/2024.01.08.574346
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Courreges C
中科院分区：
文献类型：
--
作者：
Courreges C
调节性T（Treg）细胞对于维持免疫耐受性是必不可少的，但其维持和效应子功能所需的分子组分仍然不完全确定。Treg细胞中VPS34的失活导致早期致死表型，具有大量效应T细胞活化和炎症，就像完全缺乏Treg细胞的小鼠一样。然而，VPS34缺陷型Treg细胞在体外正常发育，分布于外周淋巴器官并有效抑制常规T细胞。我们的数据表明，VPS34是维持正常数量的成熟Treg所必需的。在功能上，我们观察到VPS34活性的缺乏损害转内吞作用后的货物加工，缺陷性自噬可能有助于但不足以解释这种致死表型，并且VPS34活性的丧失诱导代谢活性升高的状态，其可能干扰Treg细胞的维持或抑制功能所需的代谢网络。
Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cellsin vitro. Our data suggest that VPS34 is required for the maintaining normal numbers of mature Treg. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy may contribute to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells.
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DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY
DOI：
10.1073/pnas.1205305109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Willinger, Tim;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
9.7
作者：
Dowling SD;Macian F
通讯作者：
Macian F