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

• Published in: Science (American Association for the Advancement of Science) Vol. 386; no. 6721; p. eadi1025
• Main Authors: Barron, Jerika J, Mroz, Nicholas M, Taloma, Sunrae E, Dahlgren, Madelene W, Ortiz-Carpena, Jorge F, Keefe, Matthew G, Escoubas, Caroline C, Dorman, Leah C, Vainchtein, Ilia D, Chiaranunt, Pailin, Kotas, Maya E, Nowakowski, Tomasz J, Bender, Kevin J, Molofsky, Ari B, Molofsky, Anna V
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 01-11-2024
• Subjects: Ablation; Allergies; Anatomy; Animals; Brain; Brain - growth & development; Brain - immunology; CD4 antigen; Central nervous system; Cerebral cortex; Cognition; Cytokines; Diphtheria; Electrophysiology; Excitability; Female; Flow cytometry; Gene sequencing; Genes; Homeostasis; Immune system; Immunity; Immunity, Innate; Immunological memory; Immunological synapses; Injection; Innate immunity; Interleukin 13; Interleukin 5; Interleukin-13 - immunology; Interleukin-13 - metabolism; Interleukins; Interneurons - metabolism; Interneurons - physiology; Interpersonal Relationship; Lymphocytes; Lymphocytes - immunology; Lymphocytes B; Lymphocytes T; Macrophages; Meninges; Meninges - immunology; Mental disorders; Mice; Mice, Inbred C57BL; Microglia; Neural networks; Neurodevelopment; Neurodevelopmental disorders; Neurons; Neurotransmitters; Postpartum period; Prefrontal cortex; Receptors; Ribonucleic acid; RNA; Signal Transduction; Social Behavior; Synapses; Synapses - physiology; Toxins
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.adi1025

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.