第 2 组先天性淋巴细胞促进抑制性突触的发育和社交行为

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-11-01 DOI:10.1126/science.adi1025

Jerika J. Barron, Nicholas M. Mroz, Sunrae E. Taloma, Madelene W. Dahlgren, Jorge F. Ortiz-Carpena, Matthew G. Keefe, Caroline C. Escoubas, Leah C. Dorman, Ilia D. Vainchtein, Pailin Chiaranunt, Maya E. Kotas, Tomasz J. Nowakowski, Kevin J. Bender, Ari B. Molofsky, Anna V. Molofsky

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引用次数: 0

摘要

先天性免疫系统影响大脑发育，并与神经发育疾病有关。确定相关的免疫细胞和信号及其对大脑回路的影响至关重要。在这项研究中，我们发现第2群先天性淋巴细胞（ILC2s）及其细胞因子白细胞介素-13（IL-13）直接向抑制性中间神经元发出信号，以增加发育中小鼠大脑的抑制性突触密度。ILC2s在发育中的脑膜中扩大并产生IL-13。失去ILC2s或IL-13对中间神经元的信号传导会减少大脑皮层的抑制性突触，但不会减少兴奋性突触。相反，ILC2s和IL-13足以增加抑制性突触。这种信号通路的缺失会导致社交互动的选择性障碍。这些数据定义了生命早期塑造抑制性突触发育和行为的2型神经免疫回路。

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

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.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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