Year: 2024
Type: article
Abstract: The innate immune system plays essential roles in brain synaptic development, and immune dysregulation is implicated in neurodevelopmental diseases. Here we show that a subset of innate lymphocytes (group 2 innate lymphoid cells, ILC2s) is required for cortical inhibitory synapse maturation and adult social behavior. ILC2s expanded in the developing meninges and 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 where as ILC2 transplant was sufficient to increase inhibitory synapse numbers. Deletion of the IL-4/IL-13 receptor ( Il4ra ) from inhibitory neurons phenocopied the reduction inhibitory synapses. Both ILC2 deficient and neuronal Il4ra deficient animals had similar and selective impairments in adult social behavior. These data define a type 2 immune circuit in early life that shapes adult brain function. One sentence summary Type 2 innate lymphoid cells and Interleukin-13 promote inhibitory synapse development.
Source: Science
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Brain and Behavior Research Foundation, Vetenskapsrådet, National Institutes of Health, University of California, Davis, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Defining lymphocyte-microglia crosstalk during cortical synapse development, Molecular and Cellular Immunology, Defining group 2 innate lymphoid cell lung niches, BD FACSAria Fusion Cell Sorter, G4756830717, G5351157054, Astrocyte-microglial communication in developmental synapse formation, G712881263, Defining the developmental role of innate lymphocytes at the brain-immune interface, Diabetes Research Center, Microglial remodeling of the extracellular matrix in memory circuits, Predoctoral Training in Developmental Biology, The function of SCN2A in neocortex, Distinct early and late programs of fibroblast - immune crosstalk govern functional responses to brain injury, Developmental Timing During Cortical Development, Meningeal type 2 immunity in cortical synapse remodeling during brain development and injury, Localization and function of tissue type 2 lymphocytes during mixed inflammation, Predoctoral Training in Neurobiology, Defining the role of tuft cells in allergic airway disease, Directed Evolution of Novel AAVs and Regulatory Elements for Selective Microglial Gene Expression
OpenAlex ID: W4403925072