Dynamic regulation of neuroinflammation and IL-1b-trap

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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.