Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, China.
Elife. 2023 Sep 20;12:RP86591. doi: 10.7554/eLife.86591.
Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here, we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term , and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver, and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.
在成年人中，数十亿凋亡细胞每天都会被专业吞噬细胞（如巨噬细胞）和邻近的非专业吞噬细胞（如基质细胞）清除。尽管中性粒细胞是一种专业吞噬细胞，但人们认为它被排除在凋亡部位之外，以避免组织炎症。在这里，我们报告了中性粒细胞作为主要吞噬细胞清除稳定状态下凋亡肝细胞的基本和意外作用。与巨噬细胞吞噬死亡细胞不同，中性粒细胞直接钻入凋亡的肝细胞中，我们将这一过程称为 ，并从内部吞噬坏死细胞。中性粒细胞的耗竭导致凋亡小体的清除缺陷，诱导小鼠肝脏组织损伤，并导致自身抗体的产生。人类自身免疫性肝病显示出中性粒细胞介导的清除凋亡肝细胞的类似缺陷。因此，中性粒细胞通过穿孔作用具有一种专门的、免疫沉默的清除凋亡肝细胞的机制，而中性粒细胞这一关键的管家功能缺陷导致了自身免疫性肝病的发生。
