| First Author | Jiang D | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 12 | Pages | 2318-2335.e7 |
| PubMed ID | 36379210 | Mgi Jnum | J:333421 |
| Mgi Id | MGI:7413821 | Doi | 10.1016/j.immuni.2022.10.018 |
| Citation | Jiang D, et al. (2022) Neuronal signal-regulatory protein alpha drives microglial phagocytosis by limiting microglial interaction with CD47 in the retina. Immunity 55(12):2318-2335.e7 |
| abstractText | 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 (SIRPalpha) is a permissive cue for microglial phagocytosis in the developing murine retina. Removal of neuronal, but not microglial, SIRPalpha reduced microglial phagocytosis, increased synpase numbers, and impaired circuit function. Conversely, prolonging neuronal SIRPalpha expression extended developmental microglial phagocytosis. These outcomes depended on the interaction of presynaptic SIRPalpha with postsynaptic CD47. Global CD47 deficiency modestly increased microglial phagocytosis, while CD47 overexpression reduced it. This effect was rescued by coexpression of neuronal SIRPalpha or codeletion of neuronal SIRPalpha and CD47. These data indicate that neuronal SIRPalpha regulates microglial phagocytosis by limiting microglial SIRPalpha access to neuronal CD47. This discovery may aid our understanding of synapse loss in neurological diseases. |
