Grant: Project Grant

Immune-based therapies are widely applied, and it becomes important to understand the range of normal functions the immune system performs to avoid serious side effects or complications. Interleukin 17 (IL-17), an immune mediated cytokine, has been successfully targeted for treating a range of human diseases. Recently, IL-17 level was found to be abnormal in people with treatment-resistant depression, and IL-17 became a target of an on-going clinical trial. However, any role of IL-17 in regulating normal brain physiology is poorly understood. We have evidence that suggests IL-17 may be important for how we respond to stress, especially in females. Stress is an integral part of daily life but too much stress often exacerbates preexisting conditions or illnesses, delaying recovery processes. As such, a healthy response to stress is essential for wellbeing. The response to stress is evolutionarily conserved and shows substantial sex differences which is not completely understood. The goal of our proposal is to understand how IL-17 influence the response to stress using a rodent model in both males and females. We will try to understand what cells of the brain are involved and how we may selectively target them. We will also study how females and males differ in their responses to stress and why IL-17 may account for at least some of the sex differences. To achieve our goal, we have put together a team of immunologists and computational biologist with expertise in IL-17 biology. We developed novel transgenic animals and will take a multi-pronged approach to investigate the stress response at molecular, cellular, endocrine, and animal behavioral levels.