Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3

Zhang, Xingli; Wang, Yan; Jia, Yuan; Ni, Li; Pei, Siyu; Xu, Jing; Luo, Xuan; Mao, Chaoming; Liu, Junli; Yu, Tao; Gan, Shucheng; Qin, Zheng; Liang, Yinming; Guo, Weixiang; Qiu, Ju; Constantin, Gabriela; Jin, Jin; Qin, Jun; Xiao, Yichuan

doi:10.1084/jem.20171417

Cited by 140 publications

(142 citation statements)

References 48 publications

(83 reference statements)

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“…GSEA results implicate the NF-κB pathway as the most affected signaling pathway, with more than 150 NF-κB target genes upregulated in Socs3-deficient neutrophils in response to G-CSF compared with Socs3 fl/fl mice. Previous studies have suggested that Socs3 negatively regulates the NF-κB pathway in macrophages (80), and our data suggest that Socs3 may also negatively regulate the NF-κB pathway in neutrophils. The RNA-Seq data also demonstrate that the STAT5 pathway, which GM-CSF activates, is enhanced in Socs3-deficient neutrophils after an 8-hour stimulation with G-CSF.…”

Section: Discussionsupporting

confidence: 76%

Deficiency of Socs3 leads to brain-targeted experimental autoimmune encephalomyelitis via enhanced neutrophil activation and ROS production

Yan¹,

Yang²,

Parkitny³

et al. 2019

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Section: Discussionsupporting

confidence: 76%

Deficiency of Socs3 leads to brain-targeted experimental autoimmune encephalomyelitis via enhanced neutrophil activation and ROS production

Yan¹,

Yang²,

Parkitny³

et al. 2019

JCI Insight

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“…Whereas, removal of this histone mark is mediated by the H3K27me3 demethylases KDM6A and KDM6B. Zhang et al reported the critical role of the EZH2 histone methyltransferase modification in altering macrophage phenotype (203). EZH2 controls H3K27me3 deposition on the promoter of SOCS3, that encodes a cytokine signaling repressor.…”

Section: Epigenetic Control Of Macrophage Polarizationmentioning

confidence: 99%

Mechanisms of Macrophage Polarization in Insulin Signaling and Sensitivity

et al. 2020

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Type-2 diabetes (T2D) is a disease of two etiologies: metabolic and inflammatory. At the cross-section of these etiologies lays the phenomenon of metabolic inflammation. Whilst metabolic inflammation is characterized as systemic, a common starting point is the tissue-resident macrophage, who's successful physiological or aberrant pathological adaptation to its microenvironment determines disease course and severity. This review will highlight the key mechanisms in macrophage polarization, inflammatory and non-inflammatory signaling that dictates the development and progression of insulin resistance and T2D. We first describe the known homeostatic functions of tissue macrophages in insulin secreting and major insulin sensitive tissues. Importantly we highlight the known mechanisms of aberrant macrophage activation in these tissues and the ways in which this leads to impairment of insulin sensitivity/secretion and the development of T2D. We next describe the cellular mechanisms that are known to dictate macrophage polarization. We review recent progress in macrophage bio-energetics, an emerging field of research that places cellular metabolism at the center of immune-effector function. Importantly, following the advent of the metabolically-activated macrophage, we cover the known transcriptional and epigenetic factors that canonically and non-canonically dictate macrophage differentiation and inflammatory polarization. In closing perspectives, we discuss emerging research themes and highlight novel non-inflammatory or non-immune roles that tissue macrophages have in maintaining microenvironmental and systemic homeostasis.

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“…5 In certain contexts, EZH2 is implicated as a negative regulator of innate immune signaling associated with viral sensing in part through inhibition of RIG-I or with degradation of TRAF6. 45,46 KDM6B regulates several transcription factors of the innate immune response, and its expression is increased by NF-kB in response to microbial stimuli. 47 In MDS patients, KDM6B mediates transcription of multiple genes involved in NF-kB activation, suggesting that KDM6B is a feedforward activation node of innate immune signaling in HSPCs.…”

Section: Functional Evidence Of Innate Immune Signaling Dysregulationmentioning

confidence: 99%

Chronic immune response dysregulation in MDS pathogenesis

Barreyro

Chlon

Starczynowski

2018

Blood

168

166

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Chronic innate immune signaling in hematopoietic cells is widely described in myelodysplastic syndromes (MDS), and innate immune pathway activation, predominantly via pattern recognition receptors, increases the risk of developing MDS. An inflammatory component to MDS has been reported for many years, but only recently has evidence supported a more direct role of chronic innate immune signaling and associated inflammatory pathways in the pathogenesis of MDS. Here we review recent findings and discuss relevant questions related to chronic immune response dysregulation in MDS.

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Macrophage/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3

Cited by 140 publications

References 48 publications

Deficiency of Socs3 leads to brain-targeted experimental autoimmune encephalomyelitis via enhanced neutrophil activation and ROS production

Deficiency of Socs3 leads to brain-targeted experimental autoimmune encephalomyelitis via enhanced neutrophil activation and ROS production

Mechanisms of Macrophage Polarization in Insulin Signaling and Sensitivity

Chronic immune response dysregulation in MDS pathogenesis

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