A body-brain circuit regulating body inflammatory responses

The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function, metabolism and nutritional state. Here, we show that a peripheral immune insult powerfully activates the body-brain axis to regulate immune responses. We demonstrate that pro- and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-to-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords exceptional neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuro-immune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.

体脑轴（body-brain axis）正逐渐成为机体生理活动的核心调控枢纽，可感知并调控器官功能、代谢与营养状态。本研究发现，外周免疫损伤可强力激活体脑轴以调控免疫应答。研究证实，促炎与抗炎细胞因子可分别靶向不同亚群的迷走神经元（vagal neurons），向大脑传递正在发生的炎症应答信号；反之，大脑则会精准调控外周免疫应答的进程。对该体脑传导通路进行基因沉默后，会引发免疫应答失调、炎症反应失控；与之相反，激活而非沉默该通路，则可实现对免疫应答的精准高效神经调控。本研究通过单细胞RNA测序（single-cell RNA sequencing）结合功能成像（functional imaging）技术，解析了该神经免疫轴（neuro-immune axis）的通路组成，并证实对其进行选择性操控，可在增强抗炎状态的同时有效抑制促炎反应。大脑介导的免疫应答进程重塑，为干预多种免疫失调类疾病——从自身免疫疾病、细胞因子风暴（cytokine storm）到感染性休克——提供了全新思路。