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

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

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

Source

Jiang D, Burger CA, Akhanov V, Liang JH, Mackin RD, Albrecht NE, Andrade P, Schafer DP, Samuel MA. Neuronal signal-regulatory protein alpha drives microglial phagocytosis by limiting microglial interaction with CD47 in the retina. Immunity. 2022 Dec 13;55(12):2318-2335.e7. doi: 10.1016/j.immuni.2022.10.018. Epub 2022 Nov 14. PMID: 36379210; PMCID: PMC9772037.

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DOI
10.1016/j.immuni.2022.10.018
PubMed ID
36379210
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