Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior [snRNA-Seq]

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. Here we show that group 2 innate lymphoid cells (ILC2s) and their cytokine Interleukin-13 (IL-13) signal directly to inhibitory interneurons to increase inhibitory synapse density in the developing 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 30 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. Overall design: Single nucleus gene expression profiling of cortical interneurons comparing the transcriptional effect of IL-13 versus saline exposure at postnatal day 15.