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

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

Author information

1
Department of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
2
Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
3
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
4
Department of Neurobiology, Stanford University, Palo Alto, CA, USA.
5
Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
6
Department of Otolaryngology, University of California, San Francisco, San Francisco, CA, USA.
7
Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan.
8
Research Center for Next Generation Medicine, Shinshu University, Matsumoto, Japan.
9
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
10
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA. anna.molofsky@ucsf.edu ari.molofsky@ucsf.edu.
11
Department of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. anna.molofsky@ucsf.edu ari.molofsky@ucsf.edu.

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.

PMID:
29420261
PMCID:
PMC6070131
DOI:
10.1126/science.aal3589
[Indexed for MEDLINE]
Free PMC Article

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