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Immune cell regulation of glia during CNS injury and disease

Abstract

Glial cells are abundant in the CNS and are essential for brain development and homeostasis. These cells also regulate tissue recovery after injury and their dysfunction is a possible contributing factor to neurodegenerative and psychiatric disease. Recent evidence suggests that microglia, which are also the brain’s major resident immune cells, provide disease-modifying regulation of the other major glial populations, namely astrocytes and oligodendrocytes. In addition, peripheral immune cells entering the CNS after injury and in disease may directly affect microglial, astrocyte and oligodendrocyte function, suggesting an integrated network of immune cell–glial cell communication.

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Fig. 1: CNS resident cell types.
Fig. 2: Context-dependent signalling of microglia to astrocytes and oligodendrocytes.
Fig. 3: Peripheral immune cell infiltration and their dynamic interaction with microglia after CNS injury.

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Acknowledgements

The authors thank the all the scientists involved in producing the original work and we hope we have done justice to their findings.

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A.D.G. and F.C.B. researched data for the article and made substantial contributions to the discussion of the content. All the authors contributed equally to writing the article and to the review and editing of the manuscript before submission.

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Correspondence to Andrew D. Greenhalgh.

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Nature Reviews Neuroscience thanks O. Butovsky, J. Schwab and B. Stevens for their contribution to the peer review of this work.

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Glossary

Macrophages

Phagocytic immune cells involved in homeostasis and inflammation. They may be tissue resident or recruited from circulating monocyte populations to sites of inflammation.

Genome-wide association studies

Studies that integrate whole genomes across populations to identify genetic variants in individuals and associate those variants with a trait.

Lymphatic system

A vascular network that drains fluid from the extracellular space and traffics this and immune cells to lymphoid organs and the systemic circulation.

Adaptive immune cell

A T cell or B cell that can acquire and maintain specific knowledge of non-self-pathogens (or self-antigens during disease) to mount a specific immune response.

Neutrophils

Innate immune cells that are often the first recruits to sites of inflammation, where they release antimicrobial agents, enzymes, nitrogen oxides and other proteins.

Monocytes

Cells that develop in the bone marrow, are released into the circulation and can be recruited during inflammation. Monocytes give rise to monocyte-derived cells such as macrophages (but are often functionally distinct from tissue-resident macrophage populations).

Dendritic cells

Antigen-presenting cells that exert immune surveillance for exogenous and endogenous antigens for the activation of naive T cells giving rise to various immunological responses.

Innate lymphoid cells

Immune cells that belong to the lymphoid lineage but do not express antigen-specific receptors and are therefore involved in innate immune regulation of homeostasis and inflammation.

Lymphocyte

A cell that is derived from a haematopoietic stem cell. Lymphocytes ultimately form the cells of the adaptive immune system.

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Greenhalgh, A.D., David, S. & Bennett, F.C. Immune cell regulation of glia during CNS injury and disease. Nat Rev Neurosci 21, 139–152 (2020). https://doi.org/10.1038/s41583-020-0263-9

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