Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development

Science. 2018 Mar 16;359(6381):1269-1273. doi: 10.1126/science.aal3589. Epub 2018 Feb 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Central Nervous System / growth & development*
  • Central Nervous System / metabolism
  • Homeostasis
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism*
  • Mice
  • Mice, Knockout
  • Microglia / physiology*
  • Nerve Net / growth & development*
  • Neurogenesis*
  • Sensorimotor Cortex / growth & development
  • Sensorimotor Cortex / physiology
  • Synapses / physiology*
  • Thalamus / abnormalities


  • Il33 protein, mouse
  • Interleukin-33