CSF1R Ligands IL-34 and CSF1 Are Differentially Required for Microglia Development and Maintenance in White and Gray Matter Brain Regions
| Autor: | Robby M. Weimer, Ali A. Zarrin, Courtney Easley-Neal, Oded Foreman, Neeraj Sharma |
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| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Immunology microglia Mice Transgenic Receptor tyrosine kinase Colony stimulating factor 1 receptor 03 medical and health sciences Mice 0302 clinical medicine Csf1 medicine Immunology and Allergy Animals Csf1r Gray Matter Tissue homeostasis Original Research biology Microglia Interleukins Macrophage Colony-Stimulating Factor Embryo White Matter Cell biology White (mutation) 030104 developmental biology medicine.anatomical_structure Drug development Receptors Granulocyte-Macrophage Colony-Stimulating Factor IL-34 biology.protein Antibody CNS lcsh:RC581-607 030215 immunology Signal Transduction |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| ISSN: | 1664-3224 |
| Popis: | Microglia are specialized brain macrophages that play numerous roles in tissue homeostasis and response to injury. Colony stimulating factor 1 receptor (CSF1R) is a receptor tyrosine kinase required for the development, maintenance, and proliferation of microglia. Here we show that in adult mice peripheral dosing of function-blocking antibodies to the two known ligands of CSF1R, CSF1, and IL-34, can deplete microglia differentially in white and gray matter regions of the brain, respectively. The regional patterns of depletion correspond to the differential expression of CSF1 and IL-34. In addition, we show that while CSF1 is required to establish microglia in the developing embryo, both CSF1 and IL-34 are required beginning in early postnatal development. These results not only clarify the roles of CSF1 and IL-34 in microglia maintenance, but also suggest that signaling through these two ligands might support distinct sub-populations of microglia, an insight that may impact drug development for neurodegenerative and other diseases. |
| Databáze: | OpenAIRE |
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