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    Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development. Vainchtein Ilia D,Chin Gregory,Cho Frances S,Kelley Kevin W,Miller John G,Chien Elliott C,Liddelow Shane A,Nguyen Phi T,Nakao-Inoue Hiromi,Dorman Leah C,Akil Omar,Joshita Satoru,Barres Ben A,Paz Jeanne T,Molofsky Ari B,Molofsky Anna V Science (New York, N.Y.) 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. 10.1126/science.aal3589