罗格斯大学Brian P. Daniels研究组在研究中取得进展。他们揭示了RIPK3激酶通过抑制中枢神经系统病毒感染期间的兴奋性神经传递来促进神经元存活。相关论文于2025年2月24日发表在《免疫学》杂志上。

课题组研究人员发现受体相互作用蛋白激酶3 （RIPK3）通过抑制兴奋性神经传递来保护黄病毒感染期间神经元的存活。这些作用独立于RIPK3在促进坏死下垂和炎症转录方面的传统功能。相反，RIPK3促进神经元调节激酶钙/钙调素依赖性蛋白激酶II （CaMKII）的磷酸化，进而激活转录因子环AMP反应元件结合蛋白（CREB）来驱动神经保护转录程序并抑制deleteriothem谷氨酸能信号传导。这些发现确定了典型细胞死亡蛋白在病毒感染期间通过调节神经元活动促进神经元存活的意想不到的功能，突出了神经免疫串扰的机制。

据了解，虽然最近的工作已经确定了免疫介质在调节神经活动中的作用，但神经元内的先天免疫信号如何影响神经传递仍然知之甚少。新出现的证据表明，神经传递的调节可能在中枢神经系统感染期间的宿主保护中起重要作用。

附：英文原文

Title: The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection

Author: Irving Estevez, Benjamin D. Buckley, Marissa Lindman, Nicholas Panzera, Tsui-Wen Chou, Micheal McCourt, Brandon J. Vaglio, Colm Atkins, Bonnie L. Firestein, Brian P. Daniels

Issue&Volume: 2025-02-24

Abstract: While recent work has identified roles for immune mediators in regulating neural activity, how innate immune signaling within neurons influences neurotransmission remains poorly understood. Emerging evidence suggests that the modulation of neurotransmission may serve important roles in host protection during infection of the central nervous system. Here, we showed that receptor-interacting protein kinase-3 (RIPK3) preserved neuronal survival during flavivirus infection through the suppression of excitatory neurotransmission. These effects occurred independently of the traditional functions of RIPK3 in promoting necroptosis and inflammatory transcription. Instead, RIPK3 promoted phosphorylation of the neuronal regulatory kinase calcium/calmodulin-dependent protein kinase II (CaMKII), which in turn activated the transcription factor cyclic AMP response element-binding protein (CREB) to drive a neuroprotective transcriptional program and suppress deleterious glutamatergic signaling. These findings identify an unexpected function for a canonical cell death protein in promoting neuronal survival during viral infection through the modulation of neuronal activity, highlighting mechanisms of neuroimmune crosstalk.

DOI: 10.1016/j.immuni.2025.01.017

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00066-4