Abstract # 2075 Structural and functional cytoarchitecture of IL-1R1-expressing system in the brain

Abstract

IL-1R1 signaling is important for the pathogenesis for almost all CNS diseases. Here, we demonstrate the cell-type specific IL-1R1 expression patterns in the brain using a knockin reporter. The functions of IL-1R1 are then investigated by selective reciprocal deletion or expression of IL-1R1 on specific cell types. Endothelial IL-1R1 is found to mediate sickness behavior, leukocyte recruitment, and inflammatory microglial activation, whereas ventricular IL-1R1 is found critical for monocyte recruitment and non-inflammatory microglial activation. In contrast, the astrocytic IL-1R1 signaling dampens inflammatory cytokines. Chronic hippocampal expression of IL-1 suppresses neurogenesis, through endothelial IL-1R1, but induces microglial activation through neuronal IL-1R1. In addition, IL-1 stimulates its own production in microglia indirectly through eIL-1R1. Collectively, these findings describe the structural and functional cytoarchitecture of the brain IL-1R1 expressing system and lay a foundation for the dissection and identification of IL-1R1 signaling pathways in the pathogenesis of numerous CNS diseases.