A Neural Thermostat Sets the Intensity of Immune Responses
Specialized neurons in the brainstem and vagus nerve provide potential therapeutic targets for treating inflammatory disorders.
Hannah joined The Scientist as an assistant editor in 2023. She earned her PhD in neuroscience from the University of Washington in 2017 and completed the Dalla Lana Fellowship in Global Journalism in 2020.
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The mammalian immune system must operate on the razor’s edge, mounting a robust inflammatory response to neutralize harmful microbes while minimizing tissue damage. A new study in Nature demonstrated that the brain helps maintain this delicate balance.1 “We grew up thinking of the brain as the center for our thoughts, our memories, our emotions,” said Charles Zuker, a Columbia University neuroscientist and study author. “But that, I think, is an overly human-centric vision. It is clear that the brain really evolved to be the master controller and regulator of the body.”
In a mouse model, the researchers identified a group of neurons in the caudal nucleus of the solitary tract (cNST), a brainstem region that is a key target of the vagus nerve, that was activated by peripheral lipopolysaccharide (LPS) injection, a potent inflammatory stimulus.
Researchers then manipulated these neurons to determine their role in calibrating the response to LPS. When these neurons were silenced, the LPS-injected mice displayed an outsize inflammatory response; conversely, stimulating the neurons promoted an anti-inflammatory response.
Next, researchers performed single-cell RNA sequencing on the cNST neurons and identified dopamine β-hydroxylase (Dbh) expression as a marker for the neurons responsible for suppressing inflammation. They also identified a population of sensory neurons in the vagus nerve which transmitted information about peripheral inflammation to the brain and activated the DBH neurons. Stimulating this subset of vagal neurons reduced inflammation in mouse models of sepsis and ulcerative colitis, improving survival and reducing tissue damage.
“I think the paper is amazing,” said Luis Ulloa, a neuroimmunologist at Duke University who was not involved in the study. While the anti-inflammatory effects of vagus nerve stimulation were previously known, Ulloa likened this study to the information board in a train station, providing details about where certain signals are coming from and going to, potentially enabling more targeted treatments in the future.
Disclosure of conflicts of interest: Charles Zuker is a co-inventor in a patent application describing this work and a co-founder of Nilo Therapeutics.
Reference
1. Jin H, et al. Nature. 2024;630(8017):695-703.
