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Microglia Diversity in Health and Multiple Sclerosis
Sameera Zia1, Khalil S Rawji2, Nathan J Michaels3
1Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Abstract:
Multiple Sclerosis (MS) is a neurodegenerative disease characterized by multiple focal lesions, ongoing demyelination and, for most people, a lack of remyelination. MS lesions are enriched with monocyte-derived macrophages and brain-resident microglia that, together, are likely responsible for much of the immune-mediated neurotoxicity. However, microglia and macrophage also have documented neuroprotective and regenerative roles, suggesting a potential diversity in their functions. Linked with microglial functional diversity, they take on diverse phenotypes developmentally, regionally and across disease conditions. Advances in technologies such as single-cell RNA sequencing and mass cytometry of immune cells has led to dramatic developments in understanding the phenotypic changes of microglia and macrophages. This review highlights the origins of microglia, their heterogeneity throughout normal ageing and their contribution to pathology and repair, with a specific focus on autoimmunity and MS. As phenotype dictates function, the emerging heterogeneity of microglia and macrophage populations in MS offers new insights into the potential immune mechanisms that result in inflammation and regeneration.
Insights
Multiple Sclerosis (MS) involves immune cells like microglia and macrophages. Their diverse functions in neuroinflammation and repair offer new therapeutic targets for this neurodegenerative disease.
Area of Science:
- Neuroimmunology
- Neurodegeneration
Background:
- Multiple Sclerosis (MS) is a neurodegenerative disease marked by demyelination and lesions.
- Monocyte-derived macrophages and microglia accumulate in MS lesions, contributing to neurotoxicity.
- These immune cells also possess neuroprotective and regenerative functions, indicating functional diversity.
Purpose of the Study:
- To review the origins, heterogeneity, and functional diversity of microglia and macrophages.
- To explore their roles in normal aging, autoimmunity, and specifically Multiple Sclerosis (MS).
- To highlight how understanding immune cell phenotypes can reveal mechanisms of inflammation and regeneration in MS.
Main Methods:
- Review of existing literature on microglia and macrophage biology.
- Integration of findings from advanced technologies like single-cell RNA sequencing and mass cytometry.
- Focus on phenotypic changes in immune cells within the context of MS pathology.
Main Results:
- Microglia and macrophages exhibit significant phenotypic heterogeneity across development, regions, and disease states.
- These immune cells are implicated in both the neurotoxicity and potential repair mechanisms in MS.
- Emerging data reveals diverse functional states of these cells in MS.
Conclusions:
- The functional diversity of microglia and macrophages is critical to understanding MS.
- Phenotypic heterogeneity offers new insights into immune-driven inflammation and regeneration in MS.
- Targeting specific microglia and macrophage phenotypes may present novel therapeutic strategies for MS.
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