GABA 能突触通过胰岛素信号抑制. 的肠道固有免疫。
GABAergic synapses suppress intestinal innate immunity via insulin signaling in .
机构信息
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, 410082 Changsha, China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, China.
出版信息
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2021063118.
GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAR-deficient mutant compared with wild-type animals. with knockdown or loss of function exhibited enhanced resistance to PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse-muscular insulin-intestinal innate immunity in vivo.
GABA 能神经传递构成了主要的抑制性信号机制，在中枢神经系统生理学和免疫细胞免疫调节中发挥着关键作用。然而，其在先天免疫中的作用尚不清楚。在这里，我们报告说，缺失会导致对病原体的抵抗力增强，而病原体感染会增强 GABA 能传递的强度。GABA 能突触以一种依赖于 FOXO/DAF-16 而不是 p38/PMK-1 途径的方式控制先天免疫。我们的数据显示，与野生型动物相比，GABAR 缺陷型突变体的 GABA 能神经肌肉接头中的胰岛素样肽 INS-31 水平显著降低。用 敲低或功能丧失会导致对 PA14 暴露的抵抗力增强。INS-31 可能在下丘脑 GABA 能 NMJ 和体壁肌肉中发挥作用，以非细胞自主的方式控制肠道先天免疫。我们的结果揭示了体内突触-肌肉胰岛素-肠道先天免疫的信号轴。
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