What controls our body’s immune response?

Brainstem neurons identified as regulators of inflammation.


Researchers at the Feinstein Institutes for Medical Research — the global scientific home of bioelectronic medicine — discovered that a small cluster of neurons within the brain is responsible for controlling the body’s immune response and cytokines, which leads to inflammation in the body. 

This discovery, published yesterday in Proceedings of the National Academy of Sciences of the United States of America (PNAS), adds to the growing body of research in the field of bioelectronic medicine and, more specifically, how the brain regulates the body’s immune response.

Bioelectronic medicine explores the use of electronic devices to treat diseases and injury instead of drugs while reducing significant side effects associated with drugs. Bioelectronic medicine aims to identify neural targets that can be selectively activated or inhibited when needed; that, in turn, controls specific organs’ function.

One area of study is how the vagus nerve, the longest nerve in the body that controls organs’ physiology like the heart, the intestines, and the liver, can be targeted to treat conditions like heart failure, hypertension, rheumatoid arthritis, and lupus. Once neural targets are identified, scientists and engineers can build bioelectronic devices to modulate that neural target activity.

This new research, led by Sangeeta S. Chavan, Ph.D., professor at the Feinstein Institutes, reveals a population of neurons in the brainstem dorsal motor nucleus (DMN) of the vagus are responsible for communicating cytokine-inhibiting signals to the splenic nerve. By controlling these neural signals through selective stimulation, researchers can turn off cytokines and other proteins that affect the body’s immune response, which accounts for many inflammatory diseases and autoimmune disorders.

“Think of the vagus nerve as the body’s main highway that helps control the immune system. Sometimes, you can’t slow it down, which causes over-inflammation and disease,” said Dr. Chavan. “With this discovery, we are pleased to note that we can target different neural sites such as the brain, the splenic nerve, and the vagus nerve, using bioelectronic devices to control inflammation and treat illness without pharmaceuticals.”

Neural signals are sent through vagus nerve fibers in an afferent (toward the brain) or efferent (away from the brain, toward peripheral organs). To identify the vagus fiber subsets and the brain regions, Dr. Chavan and Adam Kressel, MD, a graduate student in Dr. Chavan’s lab, used a combination of anatomical and functional mapping with direct assessment of the immune response. 

Using bioelectronic devices, specifically laser light to activate neurons and micro cuff electrodes to record neural activity, their research showed that selective activation of a subset of vagus nerve fibers stemming from the brain could control the immune system response to inflammation.

“Dr. Chavan’s research helps us connect the activity between the brain, the vagus nerve, and other organs, giving us a better understanding of the source that controls inflammation,” said Kevin J. Tracey, MD, president, and CEO of the Feinstein Institutes. “We will continue to make progress in the field of bioelectronic medicine so that the most devastating diseases can be treated more effectively and without the use of drugs.”

Bioelectronic medicine breakthroughs

As the global scientific home of bioelectronic medicine, the Institute of Bioelectronic Medicine at the Feinstein Institutes converges expert scientists in molecular medicine, neuroscience, and bioengineering to study how to use devices to treat diseases and injury. Recent discoveries include a new method to observe vagal fibers activation during VNS and the use of anodal blocks to direct stimulation.

Journal Reference:
  1. Adam M. Kressel et al. Identification of a brainstem locus that inhibits tumor necrosis factor. DOI: 10.1073/pnas.2008213117
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