美国贝勒医学院Melanie A. Samuel团队近期取得重要工作进展，他们研究发现神经元信号调节蛋白α（SIRPα）通过限制视网膜中小胶质细胞与CD47的相互作用，来驱动小胶质细胞的吞噬活性。这一研究成果2022年11月14日在线发表于《免疫》杂志上。

研究人员发现，神经元信号调节蛋白α（SIRPα）在发育小鼠视网膜小胶质细胞的吞噬活性中发挥作用。去除神经元而非小胶质细胞，SIRPα减少了小胶质细胞的吞噬作用，增加了突触酶的数量，并损害了回路功能。相反，延长神经元SIRPα的表达，会延长发育中小胶质细胞的吞噬作用。这些结果取决于突触前SIRPα与突触后CD47的相互作用。整体CD47缺乏适度增加了小胶质细胞的吞噬作用，而CD47过度表达则降低了吞噬作用。这种效应通过神经元SIRPα的共表达或神经元SIRPα和CD47的共缺失得以挽救。

这些数据表明，神经元SIRPα通过限制小胶质细胞SIRPα与神经元CD47的接触来调节小胶质细胞的吞噬作用。这一发现可能有助于人们理解神经系统疾病中的突触丢失。

据介绍，小胶质细胞利用它们的吞噬活性，在精确的发育时期修剪多余的突触并完善神经回路。然而，控制这种吞噬机制的神经元信号在很大程度上仍未明确。

附：英文原文

Title: Neuronal signal-regulatory protein alpha drives microglial phagocytosis by limiting microglial interaction with CD47 in the retina

Author: Danye Jiang, Courtney A. Burger, Viktor Akhanov, Justine H. Liang, Robert D. Mackin, Nicholas E. Albrecht, Pilar Andrade, Dorothy P. Schafer, Melanie A. Samuel

Issue&Volume: 2022-11-14

Abstract: Microglia utilize their phagocytic activity to prune redundant synapses and refineneural circuits during precise developmental periods. However, the neuronal signalsthat control this phagocytic clockwork remain largely undefined. Here, we show thatneuronal signal-regulatory protein alpha (SIRPα) is a permissive cue for microglialphagocytosis in the developing murine retina. Removal of neuronal, but not microglial,SIRPα reduced microglial phagocytosis, increased synpase numbers, and impaired circuitfunction. Conversely, prolonging neuronal SIRPα expression extended developmentalmicroglial phagocytosis. These outcomes depended on the interaction of presynapticSIRPα with postsynaptic CD47. Global CD47 deficiency modestly increased microglialphagocytosis, while CD47 overexpression reduced it. This effect was rescued by coexpressionof neuronal SIRPα or codeletion of neuronal SIRPα and CD47. These data indicate thatneuronal SIRPα regulates microglial phagocytosis by limiting microglial SIRPα accessto neuronal CD47. This discovery may aid our understanding of synapse loss in neurologicaldiseases.

DOI: 10.1016/j.immuni.2022.10.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00559-3