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

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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE270237 | GEO | 2024/11/01

REPOSITORIES: GEO

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

Project description:The innate immune system plays essential roles in brain development, including the remodeling of neuronal synapses. Innate lymphocytes are the most recently discovered member of the innate immune arsenal, whose developmental expansion and activation make them potential mediators of brain-immune communication during synapse formation. 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 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.

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