Content of research

We are studying the link between stress and disease. Recently, when autoreactive T cells against central nervous system antigens were transferred to mice that had been subjected to chronic stress, the mice suddenly died. The cause of death was heart failure due to hemorrhage in the stomach and duodenum, as found with humans. Stress-specific activation of neural circuits induced microinflammation in the brain, where transferred T cells, etc. were accumulated in specific blood vessels, and a new neural circuit activated by this triggered the gastrointestinal disorder and heart failure. There have been no animal model of stress in which the molecular mechanism has been elucidated, and this model is useful for screening of new drugs for stress-induced diseases. Using this system, we also identified a group of molecules of which the expression is upregulated in specific blood vessels in the brain during stress, and antibodies against these molecules suppressed sudden death. We are also currently identifying marker candidates for autoreactive T cells in humans.

Potential for social implementation

• ・Drug screening for stress-induced diseases
• ・Search for new drug targets for the above diseases
• ・Development of biomarkers to predict stress sensitivity
• ・Application to diseases associated with microinflammation in the brain such as dementia
• ・Development of therapeutic agents for progressive multiple sclerosis

Appealing points to industry and local governments

This model has also identified a candidate target for antibody drugs, and will contribute to prevention and treatment strategies for stress-related diseases. Immune cells that induce microinflammation in the brain exist in humans, and the number of such immune cells varies among individuals. It is conceivable that people with many of these cells may be prone to stress-related diseases, and that these cells may serve as a good biomarker of stress sensitivity and a therapeutic target for stress tolerance induction.