Dynamic regulation of neuroinflammation and IL-1b-trap

项目总结 IL-1是一种主要的神经免疫调节剂。IL-1活性对这两种生理功能都很重要 以及所有中枢神经系统疾病的发病机制。IL-1的细胞来源不佳 缺乏操纵IL-1表达细胞的明确和遗传途径。我们已经创造了 IL-1-Trap小鼠用于观察表达IL-1的细胞。此外，我们还可以抑制或激活IL- 1化学遗传学方法表达的细胞。使用这一新工具，我们将：1)演示 在动态平衡和不同的神经免疫激活状态下，不同的细胞组表达IL-1 2)测定动态平衡的IL-1表达细胞在神经化学和 外周和中枢炎症刺激后的行为后果；以及3) 确定诱导的IL-1表达细胞对神经化学和行为的影响 外周和中枢性炎症挑战后的后果。

PROJECT SUMMARY IL-1 is a master neuroimmune regulator. IL-1 activity is important for both physiological functions of the brain and pathogenesis of all CNS diseases. The cellular sources of IL-1 are not well defined and genetic access to manipulating IL-1-expressing cells is lacking. We have created an IL-1-trap mouse to visualize IL-1 expressing cells. In addition, we can inhibit or activate IL- 1-expressing cells by chemogenetic methods. Using this new tool, we will: 1) demonstrate distinct sets of cells express IL-1 in homeostasis and in different neuroimmune activation conditions; 2) determine the role of homeostatic IL-1-expressing cells on the neurochemical and behavioral consequences following peripheral and central inflammatory challenge; and 3) determine the role of the induced IL-1-expressing cells on the neurochemical and behavioral consequences following peripheral and central inflammatory challenges.