Institut Pasteur, Université de Paris Cité, Inserm U1224, Microenvironment and Immunity Unit, 75015 Paris, France; Institut Pasteur, Université de Paris Cité, CNRS UMR 3571, Perception and Memory Unit, 75015 Paris, France; PhD Program, Ecole Doctorale Bio Sorbonne Paris Cité (BioSpc), Université de Paris Cité, 75005 Paris, France.
Institut Pasteur, Université de Paris Cité, Inserm U1224, Microenvironment and Immunity Unit, 75015 Paris, France.
Neuron. 2023 Aug 2;111(15):2367-2382.e6. doi: 10.1016/j.neuron.2023.05.009. Epub 2023 Jun 5.
The central nervous system regulates systemic immune responses by integrating the physiological and behavioral constraints faced by an individual. Corticosterone (CS), the release of which is controlled in the hypothalamus by the paraventricular nucleus (PVN), is a potent negative regulator of immune responses. Using the mouse model, we report that the parabrachial nucleus (PB), an important hub linking interoceptive afferent information to autonomic and behavioral responses, also integrates the pro-inflammatory cytokine IL-1β signal to induce the CS response. A subpopulation of PB neurons, directly projecting to the PVN and receiving inputs from the vagal complex (VC), responds to IL-1β to drive the CS response. Pharmacogenetic reactivation of these IL-1β-activated PB neurons is sufficient to induce CS-mediated systemic immunosuppression. Our findings demonstrate an efficient brainstem-encoded modality for the central sensing of cytokines and the regulation of systemic immune responses.
中枢神经系统通过整合个体所面临的生理和行为限制来调节全身免疫反应。皮质酮（CS）的释放受下丘脑室旁核（PVN）的控制，是免疫反应的一种强有力的负调节剂。我们使用小鼠模型报告称，臂旁核（PB）是一个将内脏传入信息与自主和行为反应联系起来的重要枢纽，它也整合了促炎细胞因子 IL-1β 的信号，以诱导 CS 反应。直接投射到 PVN 并接收迷走神经复合体（VC）输入的 PB 神经元的一个亚群对 IL-1β 作出反应，以驱动 CS 反应。这些 IL-1β 激活的 PB 神经元的药理学再激活足以诱导 CS 介导的全身免疫抑制。我们的研究结果表明，这是一种有效的脑干编码模式，用于中枢感知细胞因子和调节全身免疫反应。
