Skip to main content
eScholarship
Open Access Publications from the University of California

UCSF

UC San Francisco Electronic Theses and Dissertations bannerUCSF

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

Abstract

In early brain development, the formation and remodeling of neuronal synaptic connections is critical to forming functional neural circuits. The innate immune system plays essential roles in neurodevelopment, including in synapse remodeling, but the immune cells and signals that contribute are not well defined. 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 a subset of innate lymphocytes (group 2 innate lymphoid cells, ILC2s) populates the developing brain meninges and is required for cortical inhibitory synapse maturation and adult social behavior. ILC2s produced a surge of their canonical cytokine Interleukin 13 (IL-13) between postnatal days 5-15. Loss of ILC2s decreased cortical inhibitory synapse numbers in the postnatal period and led to impaired social recognition memory in adulthood. Postnatal administration of IL-13 or ILC2s into the brain ventricles was sufficient to drive an increase in inhibitory synapses. Deletion of the IL-4/IL-13 receptor (Il4ra) specifically from inhibitory neurons, but not myeloid cells, also reduced inhibitory synapses and impaired adult social behavior. These data define novel type 2 immune signaling that mediates lymphocyte-neuron communication in early life and shapes adult brain function.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View