Dynamic regulation of neuroinflammation and IL-1b-trap

项目摘要 IL-1是一种主要的神经免疫调节剂。IL-1活性对于两种生理功能都是重要的 和所有中枢神经系统疾病的发病机制。IL-1 β的细胞来源不充分， 缺乏操纵表达IL-1 β的细胞的明确的和遗传的途径。我们创造了 用IL-1 β诱捕小鼠观察表达IL-1 β的细胞。此外，我们可以抑制或激活IL- 通过化学发生学方法检测表达1 β的细胞。使用这个新工具，我们将：1）演示 不同类型的细胞表达IL-1 β，处于稳态和不同的神经免疫激活状态 2）确定稳态IL-1 β表达细胞在神经化学和免疫调节中的作用。 外周和中枢炎症激发后的行为后果;和3） 确定诱导的IL-1 β表达细胞对神经化学和行为的作用， 外周和中枢炎症激发后的后果。

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.