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

• 成果类型: Article
• 署名作者: 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.
• 署名单位: University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Lund University; University of California System; University of California San Francisco; Chan Zuckerberg Initiative (CZI); University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8512
• DOI: 10.1126/science.adi1025
• 发表日期: 2024-11-01
• 关键词: interferon-gamma; type-2; dysfunction; interneurons; activation; survival; immunity; memory; mice

摘要

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.