The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis.
The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis.
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DOI：
10.1111/j.1600-065x.2010.00919.x
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发表时间：
2010-07
影响因子：
8.7
通讯作者：
Edinger AL
中科院分区：
文献类型：
--
作者：
Walsh CM;Edinger AL
在过去的二十年里，密集的研究工作集中在确定凋亡信号在获得性免疫中的重要性。毫无疑问，caspase依赖的细胞凋亡在许多免疫过程中发挥着重要作用，包括淋巴细胞发育、正负选择、内稳态和自我耐受。细胞生物学家发展了关于细胞死亡的新见解，确立了其他细胞死亡模式的存在，如程序性坏死和II型/自噬细胞死亡。此外，免疫学家已经确定了许多高度依赖于细胞自噬的免疫过程，包括抗原呈递、淋巴细胞发育和功能、病原体识别和破坏以及炎症调节。在这篇综述中，我们提供了死亡受体结扎引起的细胞自噬和程序性坏死的详细机制描述，包括识别它们的方法，并将这些过程与细胞凋亡进行比较和对比。强调了这三个过程之间的串扰，因为新形成的证据表明，这种相互作用对于高效的T细胞克隆扩增至关重要。这一新的证据表明，除了细胞凋亡，自噬和程序性坏死在终止T细胞依赖的免疫反应中起着重要作用。
Intense research efforts over the last two decades have focused on establishing the significance of apoptotic signaling in adaptive immunity. Without a doubt, caspase-dependent apoptosis plays vital roles in many immune processes, including lymphocyte development, positive and negative selection, homeostasis, and self-tolerance. Cell biologists have developed new insights regarding cell death, establishing that other modes of cell death exist, such as programmed necrosis and type-II/autophagic cell death. Additionally, immunologists have identified a number of immunological processes that are highly dependent upon cellular autophagy, including antigen presentation, lymphocyte development and function, pathogen recognition and destruction, and inflammatory regulation. In this review, we provide detailed mechanistic descriptions of cellular autophagy and programmed necrosis induced in response to death receptor ligation, including methods to identify them, and compare and contrast these processes with apoptosis. The crosstalk between these three processes is emphasized as newly formulated evidence suggests that this interplay is vital for efficient T-cell clonal expansion. This new evidence indicates that in addition to apoptosis, autophagy and programmed necrosis play significant roles in the termination T-cell-dependent immune responses.