Microglia Diversity in Health and Multiple Sclerosis

Zia, Sameera; Rawji, Khalil S.; Michaels, Nathan J.; Burr, Mena; Kerr, Bradley J.; Healy, Luke M.; Plemel, Jason R.

doi:10.3389/fimmu.2020.588021

Cited by 55 publications

(47 citation statements)

References 170 publications

(277 reference statements)

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“…Here, we have chosen to focus on microglia only rather than other myeloid cells. The role of invading monocyte-derived macrophages is already well-described in CNS health and disease, [3][4][5] and although there is increasing interest in non-parenchymal CNS macrophages, it is difficult to separate out their function as these were hitherto indistinguishable from microglia. Thus, some roles currently attributed to microglia may be, at least in part, executed by perivascular, meningeal, and choroid plexus macrophages.…”

Section: Introductionmentioning

confidence: 99%

Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis

Tsouki

Williams

2021

Stem Cells

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In the inflammatory demyelinating neurodegenerative disease multiple sclerosis (MS), there is increasing interest in gray matter pathology, as neuronal loss and cortical atrophy correlate with disability and disease progression, and MS therapeutics fail to significantly slow or stop neurodegeneration. Microglia, the central nervous system (CNS)-resident macrophages, are extensively involved in white matter MS pathology, but are also implicated in gray matter pathology, similar to other neurodegenerative diseases, for which there is synaptic, axonal, and neuronal degeneration. Microglia display regional heterogeneity within the CNS, which reflects their highly plastic nature and their ability to deliver context-dependent responses tailored to the demands of their microenvironment. Therefore, microglial roles in the MS gray matter in part reflect and in part diverge from those in the white matter. The present review summarizes current knowledge of microglial involvement in gray matter changes in MS, in demyelination, synaptic damage, and neurodegeneration, with evidence implicating microglia in pathology, neuroprotection, and repair. As our understanding of microglial physiology and pathophysiology increases, we describe how we are moving toward potential therapeutic applications in MS, harnessing microglia to protect and regenerate the CNS.

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Section: Introductionmentioning

confidence: 99%

Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis

Tsouki

Williams

2021

Stem Cells

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“…It has been proven that in the animal model driven by CD8+ T cells, the microglial involvement is crucial (140). Recent studies using advanced technologies such as single-cell RNA sequencing and mass cytometry show that in EAE and MS, microglia and macrophages display complex heterogeneity that may lead to both immune-mediated inflammation and regeneration (141). In active MS lesions, the correlation between activated microglia and macrophages, demyelination, and axonal loss has been observed.…”

Section: Microglia In Neurological Disordersmentioning

confidence: 99%

Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease

Matejuk

Vandenbark²,

Offner³

2021

Front. Neurol.

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The immune system's role is much more than merely recognizing self vs. non-self and involves maintaining homeostasis and integrity of the organism starting from early development to ensure proper organ function later in life. Unlike other systems, the central nervous system (CNS) is separated from the peripheral immune machinery that, for decades, has been envisioned almost entirely as detrimental to the nervous system. New research changes this view and shows that blood-borne immune cells (both adaptive and innate) can provide homeostatic support to the CNS via neuroimmune communication. Neurodegeneration is mostly viewed through the lens of the resident brain immune populations with little attention to peripheral circulation. For example, cognition declines with impairment of peripheral adaptive immunity but not with the removal of microglia. Therapeutic failures of agents targeting the neuroinflammation framework (inhibiting immune response), especially in neurodegenerative disorders, call for a reconsideration of immune response contributions. It is crucial to understand cross-talk between the CNS and the immune system in health and disease to decipher neurodestructive and neuroprotective immune mechanisms for more efficient therapeutic strategies.

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“…Microglia, similar to MФs, show inflammatory and anti-inflammatory (alternatively) phenotypes in in vitro studies ( 77 ), and M2 phenotype microglia have subgroups including M2a, M2b, and M2c ( 78 , 79 ). However, scRNA-seq and mass cytometry findings show that microglia phenotype and gene expression patterns are associated with age and regional differences ( 80 ).…”

Section: The Role Of Microglial Cells In Multiple Sclerosis Pathogenesismentioning

confidence: 99%

The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations

2021

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Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS). Besides the vital role of T cells, other immune cells, including B cells, innate immune cells, and macrophages (MФs), also play a critical role in MS pathogenesis. Tissue-resident MФs in the brain’s parenchyma, known as microglia and monocyte-derived MФs, enter into the CNS following alterations in CNS homeostasis that induce inflammatory responses in MS. Although the neuroprotective and anti-inflammatory actions of monocyte-derived MФs and resident MФs are required to maintain CNS tolerance, they can release inflammatory cytokines and reactivate primed T cells during neuroinflammation. In the CNS of MS patients, elevated myeloid cells and activated MФs have been found and associated with demyelination and axonal loss. Thus, according to the role of MФs in neuroinflammation, they have attracted attention as a therapeutic target. Also, due to their different origin, location, and turnover, other strategies may require to target the various myeloid cell populations. Here we review the role of distinct subsets of MФs in the pathogenesis of MS and different therapeutic agents that target these cells.

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Microglia Diversity in Health and Multiple Sclerosis

Cited by 55 publications

References 170 publications

Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis

Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis

Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease

The Role of Distinct Subsets of Macrophages in the Pathogenesis of MS and the Impact of Different Therapeutic Agents on These Populations

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