Phagocytic clearance of dying cells and its implications.
Phagocytic clearance of dying cells and its implications.
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死亡细胞的吞噬清除及其影响。
DOI：
10.1111/imr.13285
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发表时间：
2023
影响因子：
8.7
通讯作者：
Ravichandran,KodiS
中科院分区：
文献类型：
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作者：
Ravichandran,KodiS
据估计，作为健康生活的一部分，每个成年人平均每天会转换大约 330±200 亿个细胞1, 2。这相当于我们体重的 0.4%。如此大量的细胞更新引出了一个问题——这些细胞是什么？为什么？造成这种情况的原因是多方面的。首先，体内有些细胞的寿命是有限的，例如中性粒细胞（〜1天）和红细胞（〜120天），也有其他细胞类型，例如许多造血细胞，寿命为几天到几周；这些电池在其使用寿命结束后需要被移除并被新电池取代。其次，在发育的许多方面，我们都会产生多余的细胞，其中只有少数被认为适合完全成熟，其余的则会死亡并需要去除；这方面的例子包括胸腺中的 T 细胞、骨髓中的 B 细胞以及大脑中的成体神经发生 1。第三，体内每天都会出现“受损”细胞，例如由于光/紫外线损伤，例如皮肤和眼睛的光感受器 3。因此，所有这些周转事件导致大量细胞基本上在所有器官和组织中经历死亡，尽管程度不同 2。虽然有许多不同形式的死亡过程，但注定要通过稳态更新而死亡的细胞主要是通过半胱天冬酶依赖性细胞凋亡过程死亡的。 4.这些垂死的细胞会发生什么？尽管每天有数十亿个垂死细胞，但当人们观察组织时，很难识别垂死细胞，即使是那些细胞更新率高的细胞。这是因为对垂死细胞的识别和清除非常有效5 6。就像有一套专门的分子和机制来诱导程序性细胞死亡一样，我们也拥有一套专门的机器来识别和清除这些垂死的细胞7。这种清除在稳态条件下发生得快速、有效，从免疫学的角度来看，是安静的8。值得注意的是，就像凋亡细胞死亡机器一样，清除过程在进化上也是高度保守的，并且对线虫、果蝇、斑马鱼、小鼠和人类已经建立了清除过程的保守组成部分 9, 10。本期免疫学评论重点关注细胞清除过程的不同方面及其对体内平衡和疾病的影响。
It is estimated that an average adult human turns over roughly 330±20 billion cells every day as part of healthy living 1, 2. This translates to 0.4% of our body mass. Such a large number for cell turnover then begs the question–what are these cells and why? The reasons for this are multi-factorial. First, there are cells in the body that have a finite life span, such as neutrophils (~ 1 day) and erythrocytes (~ 120 days), and there are also other cell types such as many hematopoietic cells that have a life span of a few days to few weeks; these need to be removed after their useful life span and replaced by new cells. Second, there are many aspects of development where we generate excess cells, of which only a few are deemed fit to progress to full maturation, and the rest undergo death and need to be removed; examples of this include development of T cells in the thymus, B cells in the bone marrow, and also adult neurogenesis in the brain 1. Third, there are also ‘damaged’cells that emerge daily in the body, such as due to light/UV damage, for example skin and photoreceptors of the eye 3. Thus, all these turnover events result in a large number of cells undergoing death essentially in all organs and tissues, albeit at different magnitude 2. Although there are many different forms of death processes, the cells that are destined die via homeostatic turnover do so primarily via the process of caspase-dependent apoptosis 4.What happens to these dying cells? Despite the billions of dying cells per day, when one looks at tissues, it is hard to recognize dying cells, even in those with high cellular turnover. This is because the recognition and clearance of dying cells is remarkably efficient 5 6. Just like there is a dedicated set of molecules and mechanisms to induce programmed cell death, we also possess a dedicated machinery to recognize and remove these dying cells 7. Such clearance under homeostasis conditions occurs quickly, efficiently, and from an immunological perspective, quietly 8. It is worth noting that just like the apoptotic cell death machinery, the clearance processes are also highly conserved evolutionarily, and studies from the nematode, flies, zebrafish, mice, and humans have established the conserved components of the clearance process 9, 10. This volume of Immunological Reviews focuses on different aspects of the cell clearance process and its implications to homeostasis and disease.