The clearance of dying cells: table for two.
The clearance of dying cells: table for two.
复制标题
DOI：
10.1038/cdd.2015.172
复制
发表时间：
2016-06
影响因子：
12.4
通讯作者：
Martinez J
中科院分区：
文献类型：
--
作者：
Green DR;Oguin TH;Martinez J
免疫系统的吞噬细胞必须不断地调查、识别并有效地清除由于发育、压力、感染或正常体内平衡而产生的数十亿细胞尸体。这一过程被称为efferocytosis，对于预防自身免疫性和炎症性疾病至关重要，组织中死细胞的持续存在是许多人类自身免疫性疾病的特征，尤其是系统性红斑狼疮。凋亡细胞胞浆增生最显著的特征是其“免疫沉默”反应。尽管吞噬细胞促进吞噬死细胞的机制已经得到了很好的研究，但协调处理摄入的尸体并指导随后的免疫反应的途径是一个越来越感兴趣的领域。最近描述的LC3（微管相关蛋白1A/ 1b -轻链3）-相关吞噬（LAP）途径为这一问题提供了一些线索。当细胞外颗粒（如死细胞）在吞噬过程中与细胞外受体结合，诱导自噬机制的易位，并最终将LC3转移到含有货物的吞噬体（称为LAPosome）时，LAP就会被触发。在这篇综述中，我们将研究efferocytosis和LAP对efferocytosis的影响，使我们能够重新想象自噬机制对先天宿主防御机制的影响。
Phagocytic cells of the immune system must constantly survey for, recognize, and efficiently clear the billions of cellular corpses that arise as a result of development, stress, infection, or normal homeostasis. This process, termed efferocytosis, is critical for the prevention of autoimmune and inflammatory disorders, and persistence of dead cells in tissue is characteristic of many human autoimmune diseases, notably systemic lupus erythematosus. The most notable characteristic of the efferocytosis of apoptotic cells is its ‘immunologically silent' response. Although the mechanisms by which phagocytes facilitate engulfment of dead cells has been a well-studied area, the pathways that coordinate to process the ingested corpse and direct the subsequent immune response is an area of growing interest. The recently described pathway of LC3 (microtubule-associated protein 1A/1B-light chain 3)-associated phagocytosis (LAP) has shed some light on this issue. LAP is triggered when an extracellular particle, such as a dead cell, engages an extracellular receptor during phagocytosis, induces the translocation of autophagy machinery, and ultimately LC3 to the cargo-containing phagosome, termed the LAPosome. In this review, we will examine efferocytosis and the impact of LAP on efferocytosis, allowing us to reimagine the impact of the autophagy machinery on innate host defense mechanisms.