Impaired autophagy, defective T cell homeostasis, and a wasting syndrome in mice with a T cell-specific deletion of Vps34.
Impaired autophagy, defective T cell homeostasis, and a wasting syndrome in mice with a T cell-specific deletion of Vps34.
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DOI：
10.4049/jimmunol.1202071
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Van Kaer L
中科院分区：
文献类型：
--
作者：
Parekh VV;Wu L;Boyd KL;Williams JA;Gaddy JA;Olivares-Villagómez D;Cover TL;Zong WX;Zhang J;Van Kaer L
Autophagy plays a critical role in multiple aspects of the immune system, including the development and function of T lymphocytes. In mammalian cells, the class III phosphoinositide 3-kinase Vps34 is thought to play a critical role in autophagy. However, recent studies have cast doubt on the role of Vps34 in autophagy, at least in certain cell types. In order to study the effects of Vps34 on autophagy in T lymphocytes, we generated mice that selectively lack Vps34 in the T cell lineage. Vps34 ablation in T cells caused profound defects in autophagic flux, resulting in accumulation of cellular organelles and apoptosis. These animals exhibited normal intrathymic development of conventional T cells, but were profoundly impaired in the intrathymic development of invariant natural killer T cells. In peripheral organs, T cell-specific ablation of Vps34 had a profound impact on T cell homeostasis and function. Furthermore, aged animals developed an inflammatory wasting syndrome characterized by weight loss, intestinal inflammation and anemia. Consistent with this phenotype, Vps34 was required for the peripheral maintenance and function of CD4+FoxP3+ regulatory T cells. Collectively, our study reveals a critical role for Vps34 in autophagy and for the peripheral homeostasis and function of T lymphocytes.
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DOI：
10.1084/jem.182.5.1567
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ma A;Datta M;Margosian E;Chen J;Horak I
通讯作者：
Horak I
DOI：
10.1084/jem.20050456
发表时间：
2005-08-15
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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Bendelac A
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