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Immune Signals Directly Modulate Brain's Emotional Circuits: Unraveling the Mechanism Behind Anxiety-Inducing Behaviors
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
DOI: https://doi.org/10.1016/j.cell.2025.03.005
Corresponding Authors: Professor Gloria Choi (MIT), Professor Jun R. Huh (Harvard Medical School)
2025.07.24 View 3364 -
Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months
A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2.
Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown.
Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques.
This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines.
The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients.
PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.”
“This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30.
-Publication:
Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1
-Profile:
Professor Eui-Cheol Shin
Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/)
Graduate School of Medical Science and Engineering
KAIST
2021.07.05 View 21162