Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities.
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.
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Related Subject Headings
- Signal Transduction
- Receptors, Interleukin-1 Type I
- Neurons
- Neuroimmunomodulation
- Microglia
- Mice, Transgenic
- Mice, Inbred C57BL
- Interleukin-1
- Immunology
- Endothelial Cells
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Signal Transduction
- Receptors, Interleukin-1 Type I
- Neurons
- Neuroimmunomodulation
- Microglia
- Mice, Transgenic
- Mice, Inbred C57BL
- Interleukin-1
- Immunology
- Endothelial Cells