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Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior

Affiliations
  • 1Department of Psychiatry and Behavioral Sciences-Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 2Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 4Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 5Kavli Institute for Fundamental Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 6Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 7Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • 8Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 9Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 10Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 11Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Published on:

October 31, 2024

Abstract

The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain. ILC2s expanded and produced IL-13 in the developing brain meninges. Loss of ILC2s or IL-13 signaling to interneurons decreased inhibitory, but not excitatory, cortical synapses. Conversely, ILC2s and IL-13 were sufficient to increase inhibitory synapses. Loss of this signaling pathway led to selective impairments in social interaction. These data define a type 2 neuroimmune circuit in early life that shapes inhibitory synapse development and behavior.