Microbiota-stimulated Interleukin-22 regulates brain neurons and protects against stress-induced anxiety
Ilanges, A.; Xia, M.; Lu, J.; Chen, L.; Shiao, R.; Wang, C.; Feng, R.; Jin, Z.; Yi, H.; Qi, Q.; Li, J.; Schneeberger, M.; Lu, B.; Friedman, J. M.; Yu, X.
Show abstract
Psychological stress and its sequelae are a major public health problem. While the immune system has been implicated in the development of stress-related disorders, how the immune signals modulate neural responses to stress is poorly understood. Contrary to our expectations, we found that the immune cytokine Interleukin (IL)-22 is the key mediator of an immune-to-brain pathway that diminishes, rather than amplifies, stress-induced anxiety. We showed that stress induced TH17 differentiation and IL-22 production in the intestine following barrier dysfunction and microbiota stimulation. IL-22 then directly signaled to septal neurons in the brain to mitigate anxiety-like behavior. Accordingly, mice treated with exogenous IL-22 showed resilience to chronic stress-induced anxiety disorders. Our study thus reveals a previously-unappreciated immune-to-brain axis that defends against psychological stress, suggesting a potential intervention strategy for stress-related mental diseases.
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