Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Benmamar‐Badel, Anouk; Owens, Trevor; Włodarczyk, Agnieszka

doi:10.3389/fimmu.2020.00430

Cited by 89 publications

(91 citation statements)

References 150 publications

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“…The population of microglial cells is heterogeneous and shows phenotypic and functional diversity (Silvin and Ginhoux, 2018). A CD11c + microglial subset is involved in myelinogenesis (Wlodarczyk et al, 2017), and several lines of evidence support specific functions and protective effects of CD11c + microglia (Benmamar-Badel et al, 2020). In our study both microglia and infiltrating CD11c + cells expressed genes involved in functions related to glial development and differentiation, whereas neuronal function was represented in microglia.…”

Section: Discussionsupporting

confidence: 53%

Dendritic Cells and Microglia Have Non-Redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

et al. 2020

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Section: Discussionsupporting

confidence: 53%

Dendritic Cells and Microglia Have Non-Redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

et al. 2020

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“…In some cases, the quantitative differentiation of markers is advised. For example, in the adult brain, subtle differences in CD45 protein amount can be detected between microglia expressing CD11b + /CD45 low and macrophages expressing CD11b + /CD45 high (Ford et al, 1995 ; Zhang et al, 2002 ; Grabert et al, 2016 ), although caution must be taken because CD45 expression increases in microglia upon inflammation and with aging (Roesch et al, 2018 ; Haage et al, 2019 ; Benmamar-Badel et al, 2020 ).…”

Section: How To Discriminate Innate From Infiltrated Macrophagesmentioning

confidence: 99%

Overview of General and Discriminating Markers of Differential Microglia Phenotypes

Jurga

Paleczna

Kuter

2020

Front. Cell. Neurosci.

607

527

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Inflammatory processes and microglia activation accompany most of the pathophysiological diseases in the central nervous system. It is proven that glial pathology precedes and even drives the development of multiple neurodegenerative conditions. A growing number of studies point out the importance of microglia in brain development as well as in physiological functioning. These resident brain immune cells are divergent from the peripherally infiltrated macrophages, but their precise in situ discrimination is surprisingly difficult. Microglial heterogeneity in the brain is especially visible in their morphology and cell density in particular brain structures but also in the expression of cellular markers. This often determines their role in physiology or pathology of brain functioning. The species differences between rodent and human markers add complexity to the whole picture. Furthermore, due to activation, microglia show a broad spectrum of phenotypes ranging from the pro-inflammatory, potentially cytotoxic M1 to the anti-inflammatory, scavenging, and regenerative M2. A precise distinction of specific phenotypes is nowadays essential to study microglial functions and tissue state in such a quickly changing environment. Due to the overwhelming amount of data on multiple sets of markers that is available for such studies, the choice of appropriate markers is a scientific challenge. This review gathers, classifies, and describes known and recently discovered protein markers expressed by microglial cells in their different phenotypes. The presented microglia markers include qualitative and semi-quantitative, general and specific, surface and intracellular proteins, as well as secreted molecules. The information provided here creates a comprehensive and practical guide through the current knowledge and will facilitate the choosing of proper, more specific markers for detailed studies on microglia and neuroinflammatory mechanisms in various physiological as well as pathological conditions. Both basic research and clinical medicine need clearly described and validated molecular markers of microglia phenotype, which are essential in diagnostics, treatment, and prevention of diseases engaging glia activation.

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“…However, the binding is barely detectable in the brain. Iba1 (or AIF1) and GFAP are markers of brain microglial cells and astrocytes, respectively [ 45 , 46 ]. Their presence in the lung and skin is due to secretion of Iba1/AIF1 by inflammatory macrophages [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo

Wan

Wang

Chang

et al. 2020

Cancers

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Synthetic Zfra4-10 and WWOX7-21 peptides strongly suppress cancer growth in vivo. Hypothetically, Zfra4-10 binds to the membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling for cytotoxic Z cell activation to kill cancer cells. Stimulation of membrane WWOX in the signaling complex by a WWOX epitope peptide, WWOX7-21, is likely to activate the signaling. Here, mice receiving Zfra4-10 or WWOX7-21 peptide alone exhibited an increased binding of endogenous tumor suppressor WWOX with ERK, C1qBP, NF-κB, Iba1, p21, CD133, JNK1, COX2, Oct4, and GFAP in the spleen, brain, and/or lung which led to cancer suppression. However, when in combination, Zfra4-10 and WWOX7-21 reduced the binding of WWOX with target proteins and allowed tumor growth in vivo. In addition to Zfra4-10 and WWOX7-21 peptides, stimulating the membrane Hyal-2/WWOX complex with Hyal-2 antibody and sonicated hyaluronan (HAson) induced Z cell activation for killing cancer cells in vivo and in vitro. Mechanistically, Zfra4-10 binds to membrane Hyal-2, induces dephosphorylation of WWOX at pY33 and pY61, and drives Z cell activation for the anticancer response. Thus, Zfra4-10 and WWOX7-21 peptides, HAson, and the Hyal-2 antibody are of therapeutic potential for cancer suppression.

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Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Cited by 89 publications

References 150 publications

Dendritic Cells and Microglia Have Non-Redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

Dendritic Cells and Microglia Have Non-Redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

Overview of General and Discriminating Markers of Differential Microglia Phenotypes

Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo

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