Activation of the Cerebrospinal Fluid-Contacting Nucleus Mitigates Systemic Inflammation Induced by Sepsis
Year: 2025
Type: article
Abstract: Reciprocal interactions between the central nervous system and immune are now recognized as critical components of the host response in sepsis. However, the precise mechanism by which the central nervous system modulates immune function remains largely elusive. The cerebrospinal fluid (CSF)-contacting nucleus (CSF-contacting nucleus) is a unique nucleus, with its neurons located in the brain parenchyma and processes extending into the CSF. Here, we demonstrate that the CSF-contacting nucleus plays a protective role in sepsis. We observed a significant Fos high expression within the CSF-contacting nucleus in response to sepsis with immunofluorescence assays. Ablation of the CSF-contacting nucleus exacerbated sepsis severity, result in levels of proinflammatory cytokines (IL-1β, IL-6, and TNFα) elevated. Conversely, chemogenetic activation of the CSF-contacting nucleus resulted in a reduction in proinflammatory cytokine (IL-1β, IL-6, and TNFα) levels while simultaneously increasing the levels of IL-10. Inhibition of the CSF-contacting nucleus specifically elevated IL-6 levels. Notably, single-cell RNA sequencing was employed to identify key components within the CSF-contacting nucleus that regulate systemic inflammation in septic mice. Our findings indicate an upregulation of immune-related genes in the CSF-contacting nucleus during sepsis. Collectively, our study underscores a significant role of the CSF-contacting nucleus in neuro-immune interactions and suggests its potential as a novel therapeutic target for immune-mediated diseases.
Source: Shock
Authors: Peng-fei Liu, Yu-han Ding, Ying Li, Yao Yan, Yi-jun Zhang, Jing Zhao, Bin Gui, Su-ming Zhang, Qing-qing Zhang, Rui Wang, Zhi-ping Wang, Li-cai Zhang
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7117457067
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