The myeloid side of the CNS

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Abstract

Microglia are known as the tissue‐resident macrophages of the central nervous system (CNS). Yet their unique ontogeny and distinguishing features endowed by the privileged nature of their environment have set them apart from other myeloid cells in the body. Microglia spectrum of activity enables their participation in the maintenance of homeostasis and disease processes via their interaction with CNS cells as well as the recruitment and stimulation of immune components. Microglia are now taking centre stage in the study of brain pathology, with a mounting body of evidence supporting their involvement in the genesis and progression of multiple CNS disorders. The study of myeloid cells in brain pathology is complicated by the presence of additional CNS‐associated macrophages found in CNS borders and the frequent infiltration of peripheral myeloid cells, in addition to microglia in the brain parenchyma. However, recent advancements in multi‐omics technologies and hosts of new disease and lineage‐tracing models have pushed the field towards more accurate characterisation of disease‐associated myeloid subsets, which accounts for their ontogeny.

In the context of this mini symposium in this issue of Brain Pathology, Zapata and colleagues explore the powerful applications of leading edge technologies such as CyTOF for in‐depth profiling of microglia heterogeneity. Beyond single cell profiling, Borst et al. and Berchtold et al. take a closer look at the pathology of multiple sclerosis and stroke, respectively, to exemplify the range of disease‐associated functions which myeloid cells display and how it shapes the immune response during disease progression. To tackle the question of which environmental factors shapes microglia activity in brain pathologies, Mossad and Erny discuss the role of the gut‐microbiota in defining their disease‐associated phenotype and in turn disease outcome. Emergence of more integrated multi‐omic studies will certainly pave the way to dissect the contribution of myeloid cells across brain pathologies.

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