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NEUROIMMUNOLOGY IN 2019

Neuroinflammation and neurodegeneration in human brain at single-cell resolution

Nature Reviews Immunology volume 20, pages 81–82 (2020)Cite this article

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Single-cell RNA sequencing and single-nucleus RNA sequencing have recently provided the opportunity to investigate cellular and molecular aspects of neuro-immune interactions in the brain with unprecedented detail. Here, we highlight the major advances in human neuroimmunology reported this year based on these cutting-edge technologies.

Key advances

  • Single-cell and single-nucleus RNA sequencing (snRNA-seq) using brain tissue from patients with multiple sclerosis revealed multiple distinct subsets of microglia; showed that the excitatory neurons of cortical layers 2-3 are most affected by the disease; and identified a subset of oligodendrocytes that express pro-inflammatory genes.

  • snRNA-seq deconvoluted progressive molecular alterations of various cell types arising during Alzheimer disease and revealed potential gender differences.

  • Epigenetic profiling of single nuclei identified enhancers that control the expression of genes underlying the identity and function of all human brain cells.

Genetic, pathology and clinical studies have shown that many neurological diseases have an essential immunological component. In addition to multiple sclerosis (MS) — a prototypic neuroinflammatory disease caused by autoreactive T cells that attack the central nervous system (CNS) — several lines of evidence indicate that Alzheimer disease and many other neurodegenerative diseases, although not inflammatory sensu strictu, feature a remarkable activation of CNS-resident macrophages, which are commonly known as microglia. Moreover, recent findings on the meningeal lymphatics have highlighted an additional layer of immune circuitry that may participate in neurological diseases1. Thus, understanding the dynamics of neuro-immune interactions within the CNS has become the focal point of many studies. Single-cell RNA sequencing (scRNA-seq) has greatly advanced the field by providing a high-resolution view of brain immune cells, such as microglia, in homeostasis, in ageing and in genetically modified mice that mimic human neurological diseases2,3,4. However, this approach requires digestion and dissociation of highly interconnected brain cells into a single-cell suspension and passage through microfluidic channels, which prevents accurate recovery and analysis of astrocytes, oligodendrocytes and various neuronal populations.

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Fig. 1: Transcriptomic changes in brain disease.

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Acknowledgements

We thank A. Swain and S. Gilfillan for helpful suggestions during the preparation of the manuscript.

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  1. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

    Marco Colonna & Simone Brioschi

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  1. Marco Colonna
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  2. Simone Brioschi
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Correspondence to Marco Colonna.

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Competing interests

M.C. receives research support from Alector, Amgen and Ono. S.B. declares no competing interests.

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Colonna, M., Brioschi, S. Neuroinflammation and neurodegeneration in human brain at single-cell resolution. Nat Rev Immunol 20, 81–82 (2020). https://doi.org/10.1038/s41577-019-0262-0

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