Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24

Yu, Tao; Gan, Shucheng; Zhu, Qingchen; Dai, Dongfang; Ni, Li; Wang, Hui; Chen, Xiaosong; Hou, Dan; Wang, Yan; Pan, Qiang; Xu, Jing; Zhang, Xingli; Liu, Junli; Pei, Siyu; Peng, Chao; Wu, Ping; Romano, Simona; Mao, Chaoming; Huang, Mingzhu; Zhu, Xiaoyan; Shen, Kunwei; Qin, Jun; Xiao, Yichuan

doi:10.1038/s41467-019-12384-2

Cited by 232 publications

(160 citation statements)

References 53 publications

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“…Stereotypically, STAT and PPAR signaling pathways are independently responsible for programming that drives suppressive functionality of myeloid cells ( 73 , 74 ), but there are studies that describe their joint interaction in programming as well ( 75 ). STAT3 signaling in myeloid cells can be initiated by tumor derived factors, including IL-10 and lactate.…”

Section: Suppressive Mechanismsmentioning

confidence: 99%

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

et al. 2020

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Tumor-mediated regulation of the host immune system involves an intricate signaling network that results in the tumor's inherent survival benefit. Myeloid cells are central in orchestrating the mechanisms by which tumors escape immune detection and continue their proliferative programming. Myeloid cell activation has historically been classified using a dichotomous system of classical (M1-like) and alternative (M2-like) states, defining general pro- and anti-inflammatory functions, respectively. Explosions in bioinformatics analyses have rapidly expanded the definitions of myeloid cell pro- and anti-inflammatory states with different combinations of tissue- and disease-specific phenotypic and functional markers. These new definitions have allowed researchers to target specific subsets of disease-propagating myeloid cells in order to modify or arrest the natural progression of the associated disease, especially in the context of tumor-immune interactions. Here, we discuss the myeloid cell contribution to solid tumor initiation and maintenance, and strategies to reprogram their phenotypic and functional fate, thereby disabling the network that benefits tumor survival.

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Section: Suppressive Mechanismsmentioning

confidence: 99%

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

et al. 2020

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“…Our data reinforce the idea that the search for immunomodulators is proving to be promising for the treatment of the endometriosis, despite the fact that there have been no definitive successes to date 96 . New advances in the modulation of the M1-M2 macrophage polarization 97,98 and in targeting NKT cells 99 will provide a foundation for more effective treatment of this disease.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

Poli-Neto

Meola

Silva

et al. 2020

Sci Rep

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Eutopic endometrium appears to be crucial for endometriosis development. Despite of the evident importance, data regarding the cellular microenvironment remain unclear. Our objective was to explore the tissue microenvironment heterogeneity, transcripts, and pathways that are enriched in all phases of the menstrual cycle by analysing publicly deposited data derived from whole transcriptome microarrays of eutopic endometria of women with and without endometriosis. A meta-analysis of the transcriptome microarrays was performed using raw data available from a public database. Eligibility criteria included eutopic endometrium samples from women with endometriosis and healthy controls without any pathological condition reported the presence of an adequately reported normal menstrual phase, and samples containing both glandular and stromal components. Raw data were processed using a robust multiarray average method to provide background correction, normalisation, and summarisation. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Cellular tissue heterogeneity was inferred using the xCell package. Differentially expressed genes were identified based on a 5% adjusted p value and a 2.0-fold change. Pathways were identified by functional enrichment based on the Molecular Signatures Database, a p value of < 5%, and an FDR q value of ≤ 25%. Genes that were more frequently found in pathways were identified using leading edge analysis. In a manner independent of cycle phase, the subpopulations of activated dendritic cells, CD4 T effector memory phenotype cells, eosinophils, macrophages M1, and natural killer T cells (NKT) were all higher in stage I-II endometriosis compared to those in healthy controls. The subpopulations of M2 macrophages and natural killer T cells were elevated in eutopic endometriums from women with stage III-IV endometriosis, and smooth muscle cells were always more prevalent in healthy eutopic endometriums. Among the differently expressed genes, FOS, FOSB, JUNB, and EGR1 were the most frequently mapped within the interaction networks, and this was independent of stage and cycle phase. The enriched pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial mesenchymal transition. PI3K AKT mTOR, TGF signalling, and interferon alpha/gamma responses were enriched exclusively in stage III-IV endometriosis. The cellular microenvironments and immune cell profiles were different between eutopic endometriums from women with stage I-II and stage III-IV endometriosis, and these differences were independent of the hormonal milieu. Specifically, a pro-inflammatory profile was predominant in stage I-II endometriosis, and M1-M2 polarization into eutopic endometrium may be crucial for the progression of the disease. The higher prevalence of NKT cells in eutopic endometriums from women with endometriosis that

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“…Mice TRIM24 floxed mice (previously described in Yu et al, 2019) were backcrossed with C57BL/6 mice for ≥6 generations. C57BL/6 background TRIM24 floxed mice were crossed with B6.C-Tg (CMV-Cre) 1Cgn/J mice (J006054; purchased from GemPharmatech Co.) to produce TRIM24 total knockout mice (termed TRIM24-KO).…”

Section: Methodsmentioning

confidence: 99%

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

Zhu

Gan

et al. 2020

Journal of Experimental Medicine

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Ubiquitination is an essential mechanism in the control of antiviral immunity upon virus infection. Here, we identify a series of ubiquitination-modulating enzymes that are modulated by vesicular stomatitis virus (VSV). Notably, TRIM24 is down-regulated through direct transcriptional suppression induced by VSV-activated IRF3. Reducing or ablating TRIM24 compromises type I IFN (IFN-I) induction upon RNA virus infection and thus renders mice more sensitive to VSV infection. Mechanistically, VSV infection induces abundant TRIM24 translocation to mitochondria, where TRIM24 binds with TRAF3 and directly mediates K63-linked TRAF3 ubiquitination at K429/K436. This modification of TRAF3 enables its association with MAVS and TBK1, which consequently activates downstream antiviral signaling. Together, these findings establish TRIM24 as a critical positive regulator in controlling the activation of antiviral signaling and describe a previously unknown mechanism of TRIM24 function.

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Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24

Cited by 232 publications

References 53 publications

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination

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