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Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
Published on: April 13, 2017
Microglia - the brain's busy bees
James C Cronk1, Jonathan Kipnis1
1Center for Brain Immunology and Glia, Department of Neuroscience and Graduate Program in Neuroscience, Medical Scientist Training Program, School of Medicine, University of Virginia Charlottesville, VA 22908 USA.
Abstract:
Recent years have seen significant changes in the way scientists view microglia and their role in health and disease. For decades, it was presumed that microglia were stationary, inactive immune cells in the brain, waiting for an immunologic insult to call them into action. In contrast, modern imaging techniques have revealed that microglia are constantly in motion, surveying their environment. Lineage tracing studies have led to the understanding that microglia are part of a larger family of cells, called tissue-resident macrophages, which arise from early yolk sac progenitors during embryogenesis and engraft nearly every organ in the body. Microglia, and all tissue-resident macrophages, rely on signaling through CD115 (the colony stimulating factor 1 receptor) for survival, primarily through the ligand, macrophage colony-stimulating factor. However, it is now understood that some microglia have a specific need for another CD115 ligand, Interleukin-34, which is only shared with Langerhans cells in the skin. In contrast to classical views, recent evidence suggests that the primary functions of microglia may occur during postnatal neurodevelopment and adult homeostasis, as absence or impairment of microglia results in a pathology separate from inflammatory immune function. In summary, these advances suggest that microglia might eventually be utilized or targeted to improve disease outcomes via encouraging or enhancing their health-promoting homeostatic functions.
Insights
Microglia, dynamic brain immune cells, are crucial for development and health, not just inflammation. Targeting their homeostatic functions offers new therapeutic potential for neurological diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia were historically viewed as stationary brain immune cells.
- Modern imaging reveals microglia are motile and survey their environment.
- Microglia are tissue-resident macrophages originating from yolk sac progenitors.
Purpose of the Study:
- To update the understanding of microglia's role beyond inflammation.
- To highlight the importance of microglia in neurodevelopment and homeostasis.
- To explore therapeutic targeting of microglial homeostatic functions.
Main Methods:
- Review of recent imaging techniques and lineage tracing studies.
- Analysis of CD115 signaling pathways, including macrophage colony-stimulating factor and Interleukin-34.
- Examination of evidence on microglial function in health and disease.
Main Results:
- Microglia are constantly active and essential for tissue health.
- CD115 signaling, particularly Interleukin-34, is vital for some microglia.
- Microglial absence or impairment causes unique pathologies, distinct from inflammation.
Conclusions:
- Microglia's primary roles are in development and maintaining brain homeostasis.
- Therapeutic strategies could leverage microglial health-promoting functions.
- Targeting microglia offers potential for improving neurological disease outcomes.
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