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

Liu, Xiaoyu ; Nemeth, Daniel P. ; McKim, Daniel B. ; Zhu, Ling ; DiSabato, Damon J. ; Berdysz, Olimpia ; Gorantla, Gowthami ; Oliver, Braedan ; Witcher, Kristina G. ; Wang, Yufen ; Negray, Christina E. ; Vegesna, Rekha S. ; Sheridan, John F. ; Godbout, Jonathan P. ; Robson, Matthew J. ; Blakely, Randy D. ; Popovich, Phillip G. ; Bilbo, Staci D. ; Quan, Ning

Immunity (Cambridge, Mass.), 2019-02, Vol.50 (2), p.317-333.e6 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities
Autor: Liu, Xiaoyu ; Nemeth, Daniel P. ; McKim, Daniel B. ; Zhu, Ling ; DiSabato, Damon J. ; Berdysz, Olimpia ; Gorantla, Gowthami ; Oliver, Braedan ; Witcher, Kristina G. ; Wang, Yufen ; Negray, Christina E. ; Vegesna, Rekha S. ; Sheridan, John F. ; Godbout, Jonathan P. ; Robson, Matthew J. ; Blakely, Randy D. ; Popovich, Phillip G. ; Bilbo, Staci D. ; Quan, Ning
Assuntos: Animals ; Astrocytes ; Astrocytes - cytology ; Astrocytes - immunology ; Astrocytes - metabolism ; Brain ; Brain - cytology ; Brain - immunology ; Brain - metabolism ; Cell Line ; Cells, Cultured ; Central nervous system ; Endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - immunology ; Endothelial Cells - metabolism ; Experiments ; Hybridization ; Interleukin ; Interleukin 1 ; Interleukin 1 receptors ; Interleukin-1 - pharmacology ; Labeling ; leukocytes ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia ; Microglia - cytology ; Microglia - immunology ; Microglia - metabolism ; Monocytes ; Myeloid cells ; Neurogenesis ; Neuroimmunomodulation - genetics ; Neuroimmunomodulation - immunology ; Neurons - cytology ; Neurons - immunology ; Neurons - metabolism ; Pathogenesis ; Physiology ; Receptors, Interleukin-1 Type I - genetics ; Receptors, Interleukin-1 Type I - immunology ; Receptors, Interleukin-1 Type I - metabolism ; Recruitment ; Rodents ; Roles ; Sickness behavior ; Signal transduction ; Signal Transduction - genetics ; Signal Transduction - immunology ; Signaling ; Studies ; Ventricle ; ventricular ; White blood cells
É parte de: Immunity (Cambridge, Mass.), 2019-02, Vol.50 (2), p.317-333.e6
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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. [Display omitted] •Brain IL-1R1 is found in endothelial and ventricular cells, astrocytes, and DG neurons•Ventricular IL-1R1 regulates monocyte recruitment•Endothelial and ventricular IL-1R1 regulates IL-1-induced microglial activation•Endothelial IL-1R1 mediates sickness behavior, leukocyte recruitment, and neurogenesis 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

United States: Elsevier Inc

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