T cell intrinsic roles of autophagy in promoting adaptive immunity.
T cell intrinsic roles of autophagy in promoting adaptive immunity.
复制标题
T 细胞自噬在促进适应性免疫中的内在作用。
DOI：
10.1016/j.coi.2010.03.005
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发表时间：
2010
影响因子：
7
通讯作者：
Bell,BryanD
中科院分区：
文献类型：
--
作者：
Walsh,CraigM;Bell,BryanD
自噬是一种古老的细胞反应，其中自噬空泡在胞质溶胶内形成，是响应于多种细胞损伤而诱导的，包括生长因子或营养素提取、细胞器损伤和错误折叠蛋白。自噬在抗原刺激后在T淋巴细胞中迅速诱导，并且自噬信号传导的阻断大大降低了T细胞克隆扩增，表明自噬主要参与促进T细胞存活。相比之下，最近发现的涉及FADD和caspase-8的负反馈回路限制了T细胞中自噬的水平。在T细胞有丝分裂过程中未能激活半胱天冬酶-8导致过度活跃的自噬和通过程序性坏死机制的细胞死亡。这些发现表明这些细胞过程之间的串扰对于T细胞活化和稳态是必不可少的。
Autophagy, an ancient cellular response where autophagic vacuoles are formed within the cytosol, is induced in response to a variety of cellular insults, including growth factor or nutrient withdrawal, organelle damage, and misfolded proteins. Autophagy is rapidly induced in T lymphocytes following antigenic stimulation and blockade of autophagic signaling greatly reduces T cell clonal expansion, suggesting that autophagy is primarily involved in promoting T cell survival. In contrast, a recently identified negative feedback loop involving FADD and caspase-8 limits the level of autophagy in T cells. Failure to activate caspase-8 during T cell mitogenesis leads to hyperactive autophagy and cellular death through a programmed necrotic mechanism. These findings suggest that crosstalk between these cellular processes is essential for T cell activation and homeostasis.