| Literature DB >> 29420261 |
Ilia D Vainchtein1, Gregory Chin1, Frances S Cho2,3, Kevin W Kelley1, John G Miller1, Elliott C Chien1, Shane A Liddelow4, Phi T Nguyen1,5, Hiromi Nakao-Inoue1, Leah C Dorman1,2, Omar Akil6, Satoru Joshita7,8, Ben A Barres4, Jeanne T Paz9,3, Ari B Molofsky10, Anna V Molofsky11.
Abstract
Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.Entities:
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Year: 2018 PMID： 29420261 PMCID： PMC6070131 DOI： 10.1126/science.aal3589
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728