A body–brain circuit that regulates body inflammatory responses

Good news! This research is a little bit dated (May of 2024).

These findings may lead to much better anti inflammatory and autoimmune disease treatments.

"The brain can direct the immune system to an unexpected degree, capable of detecting, ramping up and tamping down inflammation ...

The Zuker lab turned to a bacterial compound that sets off innate immune responses. The scientists found that giving this molecule to mice activated the caudal nucleus of the solitary tract, or cNST, which is tucked inside the brainstem. The cNST plays a major role in the body-brain axis and is the primary target of the vagus nerve.

The scientists showed that chemically suppressing the cNST resulted in an out-of-control inflammatory response to the immune insult: levels of pro-inflammatory molecules released by the immune system were more than three times higher than usual, and levels of anti-inflammatory immune compounds were roughly three times lower than normal. In contrast, artificially activating the cNST reduced pro-inflammatory molecule levels by nearly 70 percent and increased anti-inflammatory chemical levels almost tenfold. ...

The scientists identified the specific groups of neurons in the vagus nerve and in the cNST that help detect and control pro- and anti-inflammatory activity. ...

Discovering ways to control this newfound brain circuit may lead to novel therapies for common auto-immune diseases such as rheumatoid arthritis, type I diabetes, multiple sclerosis, neurodegenerative diseases, lupus, inflammatory bowel disease and Crohn's disease, as well as conditions such as long COVID syndrome, immune rejection of transplanted organs, and the potentially deadly outbursts known as cytokine storms that COVID infections can trigger. ..."

From the abstract:

"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 strongly activates the body–brain axis to regulate immune responses. We demonstrate that pro-inflammatory 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–brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune 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."

A Neural Thermostat Sets the Intensity of Immune Responses | TS Digest | The Scientist "Specialized neurons in the brainstem and vagus nerve provide potential therapeutic targets for treating inflammatory disorders."

Columbia Scientists Identify New Brain Circuit in Mice that Controls Body’s Inflammatory Reactions (original news release) "Findings uncover hidden connections between the brain and body; making use of this new brain circuit could lead to new therapies for many immune disorders"

A body–brain circuit that regulates body inflammatory responses

Labeled in red are neurons in the brainstem of a mouse that control body inflammatory responses. Labeled in blue are the brain’s other cells.

Fig. 1: Immune responses activate the brain via the vagal–brain axis.