Kavli Affiliate: Jeffrey Friedman
| Authors: Anoj Ilanges, Mengyu Xia, Junmei Lu, Lei Chen, Rani Shiao, Changchun Wang, Ru Feng, Zheyu Jin, Han Yi, Qingqing Qi, Jixi Li, Marc Schneeberger, Boxun Lu, Jeffrey M. Friedman and Xiaofei Yu
| Summary:
Summary 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. Competing Interest Statement The authors have declared no competing interest.