Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities

Immunity. 2019 Feb 19;50(2):317-333.e6. doi: 10.1016/j.immuni.2018.12.012. Epub 2019 Jan 22.


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.

Keywords: leukocytes; microglia; neurogenesis; ventricular.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Brain / cytology
  • Brain / immunology*
  • Brain / metabolism
  • Cell Line
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Interleukin-1 / pharmacology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / cytology
  • Microglia / immunology
  • Microglia / metabolism
  • Neuroimmunomodulation / genetics
  • Neuroimmunomodulation / immunology*
  • Neurons / cytology
  • Neurons / immunology
  • Neurons / metabolism
  • Receptors, Interleukin-1 Type I / genetics
  • Receptors, Interleukin-1 Type I / immunology*
  • Receptors, Interleukin-1 Type I / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology*


  • Interleukin-1
  • Receptors, Interleukin-1 Type I