Abstract
Interleukin-1 (IL-1) signaling is important for multiple potentially pathogenic processes in the central nervous system (CNS), but the cell-type-specific roles of IL-1 signaling are unclear. We used a genetic knockin reporter system in mice to track and reciprocally delete or express IL-1 receptor 1 (IL-1R1) in specific cell types, including endothelial cells, ventricular cells, peripheral myeloid cells, microglia, astrocytes, and neurons. We found that endothelial IL-1R1 was necessary and sufficient for mediating sickness behavior and drove leukocyte recruitment to the CNS and impaired neurogenesis, whereas ventricular IL-1R1 was critical for monocyte recruitment to the CNS. Although microglia did not express IL-1R1, IL-1 stimulation of endothelial cells led to the induction of IL-1 in microglia. Together, these findings describe the structure and functions of the brain's IL-1R1-expressing system and lay a foundation for the dissection and identification of IL-1R1 signaling pathways in the pathogenesis of CNS diseases. Liu et al. employ a genetic knockin reporter system in mice to track and reciprocally delete and/or express IL-1 receptor 1 (IL-1R1) in specific CNS cell types. They define cell-type-specific roles for IL-1 signaling, including an essential role for endothelial IL-1R1 in mediating sickness behavior, and provide a foundation for the dissection of IL-1R1 signaling pathways in the pathogenesis of CNS disease.
Original language | English (US) |
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Pages (from-to) | 317-333.e6 |
Journal | Immunity |
Volume | 50 |
Issue number | 2 |
DOIs | |
State | Published - Feb 19 2019 |
Keywords
- leukocytes
- microglia
- neurogenesis
- ventricular
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases