Regulation of microglia development and homeostasis
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Published on: April 13, 2017
1Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland. greter@immunology.uzh.ch
Abstract:
Microglia represent the resident macrophages of the central nervous system (CNS) and account for 10% of the adult glial cell population in the normal brain. Although microglial cells are thought to contribute to most pathological conditions including CNS infections, neuroinflammatory lesions, brain tumors, and neurodegenerative diseases, their exact role in CNS development, homeostasis, and disease remains poorly understood. In contrast to most macrophage populations, microglia survive high-dose ionizing radiation and maintain themselves locally and independently of circulating precursors in the steady state. However, controversies remain on the origin of microglia in the brain and whether they could potentially be repopulated by circulating myeloid precursors after brain injury. Microglia-targeted therapies through the use of genetically modified circulating hematopoietic cells proved to be a promising therapeutic strategy for the treatment of brain diseases. It is thus of great importance to understand the contribution and developmental cues of circulating myeloid cells as potential microglia progenitors to the adult pool of microglia in the steady state and under inflammatory conditions.
Insights
Microglia, the brain's immune cells, are crucial for CNS health and disease. Understanding their origin and potential repopulation by circulating myeloid cells is key for developing new microglia-targeted therapies for brain diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the central nervous system (CNS), constituting 10% of the adult glial population.
- Their precise roles in CNS development, homeostasis, and various pathologies like neurodegenerative diseases are not fully understood.
- Unlike other macrophages, microglia resist radiation and self-renew in the CNS, but their origin and potential repopulation by circulating cells remain debated.
Purpose of the Study:
- To investigate the origin of microglia and their potential repopulation by circulating myeloid precursors.
- To understand the contribution of circulating myeloid cells to the adult microglia pool under steady-state and inflammatory conditions.
- To inform the development of microglia-targeted therapies for brain diseases.
Main Methods:
- Review of existing literature on microglia origin and function.
- Analysis of studies on CNS immune cell dynamics.
- Discussion of potential therapeutic strategies involving circulating myeloid cells.
Main Results:
- Microglia are resident CNS macrophages with unique self-renewal properties.
- Controversy exists regarding whether circulating myeloid precursors can repopulate microglia after injury.
- Microglia-targeted therapies using modified circulating cells show therapeutic promise.
Conclusions:
- Further research is needed to clarify the origin and repopulation dynamics of microglia.
- Understanding circulating myeloid cell contributions is vital for advancing brain disease therapies.
- Targeting microglia represents a promising avenue for treating CNS disorders.
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