KAIST's Department of Brain and Cognitive Sciences, led by Professor Jeong-Tae Kwon, has collaborated with MIT and Harvard Medical School to make a groundbreaking discovery. For the first time globally, their joint research has revealed that cytokines, released during immune responses, directly influence the brain's emotional circuits to regulate anxiety behavior.
The study provided experimental evidence for a bidirectional regulatory mechanism: inflammatory cytokines IL-17A and IL-17C act on specific neurons in the amygdala, a region known for emotional regulation, increasing their excitability and consequently inducing anxiety. Conversely, the anti-inflammatory cytokine IL-10 was found to suppress excitability in these very same neurons, thereby contributing to anxiety alleviation.
In a mouse model, the research team observed that while skin inflammation was mitigated by immunotherapy (IL-17RA antibody), anxiety levels paradoxically rose. This was attributed to elevated circulating IL-17 family cytokines leading to the overactivation of amygdala neurons.
Key finding: Inflammatory cytokines IL-17A/17C promote anxiety by acting on excitable amygdala neurons (via IL-17RA/RE receptors), whereas anti-inflammatory cytokine IL-10 alleviates anxiety by suppressing excitability through IL-10RA receptors on the same neurons.
The researchers further elucidated that the anti-inflammatory cytokine IL-10 works to reduce the excitability of these amygdala neurons, thereby mitigating anxiety responses.
This research marks the first instance of demonstrating that immune responses, such as infections or inflammation, directly impact emotional regulation at the level of brain circuits, extending beyond simple physical reactions. This is a profoundly significant achievement, as it proposes a crucial biological mechanism that interlinks immunity, emotion, and behavior through identical neurons within the brain.
The findings of this research were published in the esteemed international journal Cell on April 17th of this year.
Paper Information:
Title: Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety
Journal: Cell (Vol. 188, 2190–2220), April 17, 2025
Corresponding Authors: Professor Gloria Choi (MIT), Professor Jun R. Huh (Harvard Medical School)