TGF‐β Control of Adaptive Immune Tolerance: A Break From Treg Cells

Liu, Ming; Li, Shun; Li, Ming O.

doi:10.1002/bies.201800063

Cited by 66 publications

(49 citation statements)

References 56 publications

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“…Higher amounts of SOCS1 protein suppress IL-12 and IFNγ signaling inhibiting Th1 cell differentiation, while promoting Th2 cell induction [78,79]. TGF-β as well promotes thymic Treg (tTreg) cell development by inducing FoxP3 expression repressing T cell clonal deletion and peripheral Treg cell differentiation [63,80]. Notably, bovine milk exosomes contain both miR-155 and TGF-β [14,32,45], a fact, that further supports milk exosome-driven maturation of tTregs [18,19].…”

Section: Allergic Diseasesmentioning

confidence: 80%

“…Two independent studies confirmed increased expression of miR-21 in placenta tissue of infants born with macrosomia (birth weight > 4000 g) [99,100]. Milk miR-21, a signature miR of commercial dairy milk and cargo of bovine milk exosomes [71,72,80], most likely reaches the placenta and increases placental and trophoblast growth. miR-21 plays important roles in growth of trophoblastic cell lines [101] and increases PI3K-AKTand mTORC1 signaling by suppression of various key inhibitory checkpoints such as PTEN [11].…”

Section: Fetal Macrosomiamentioning

confidence: 83%

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Exosomes of pasteurized milk: potential pathogens of Western diseases

Melnik

Schmitz

2019

J Transl Med

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Milk consumption is a hallmark of western diet. According to common believes, milk consumption has beneficial effects for human health. Pasteurization of cow's milk protects thermolabile vitamins and other organic compounds including bioactive and bioavailable exosomes and extracellular vesicles in the range of 40-120 nm, which are pivotal mediators of cell communication via systemic transfer of specific micro-ribonucleic acids, mRNAs and regulatory proteins such as transforming growth factor-β. There is compelling evidence that human and bovine milk exosomes play a crucial role for adequate metabolic and immunological programming of the newborn infant at the beginning of extrauterine life. Milk exosomes assist in executing an anabolic, growth-promoting and immunological program confined to the postnatal period in all mammals. However, epidemiological and translational evidence presented in this review indicates that continuous exposure of humans to exosomes of pasteurized milk may confer a substantial risk for the development of chronic diseases of civilization including obesity, type 2 diabetes mellitus, osteoporosis, common cancers (prostate, breast, liver, B-cells) as well as Parkinson's disease. Exosomes of pasteurized milk may represent new pathogens that should not reach the human food chain.

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Section: Allergic Diseasesmentioning

confidence: 80%

Section: Fetal Macrosomiamentioning

confidence: 83%

Exosomes of pasteurized milk: potential pathogens of Western diseases

Melnik

Schmitz

2019

J Transl Med

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“…Previous studies reported that tumor‐infiltrating immune cells may represent a crucial pathophysiological factor in the onset and progression of glioma . We examined the relationship between COPB2 and six immune cell types that frequently infiltrate the tumor microenvironment, including innate immune cells: neutrophils, tumor‐associated macrophages (TAMs), NK cells, and myeloid‐derived suppressor cells (MDSCs) and adaptive immune cells: CD8+T cells and regulatory T cells (Tregs) . The specific biomarker genes of each immune cell type are displayed in Data S2.…”

Section: Resultsmentioning

confidence: 99%

“…15 We examined the relationship between COPB2 and six immune cell types that frequently infiltrate the tumor microenvironment, including innate immune cells: neutrophils, tumor-associated macrophages (TAMs), NK cells, and myeloid-derived suppressor cells (MDSCs) 16,17 and adaptive immune cells: CD8+T cells and regulatory T cells (Tregs). 18,19 The specific biomarker genes of each immune cell type are displayed in Data S2. Canonical correlation analysis revealed that the transcript levels of COPB2 were positively correlated with the marker gene expression of these six immune cell types in the TCGA datasets ( Figure 5B, P < .001), indicating that glioma patients with COPB2high were prone to have more immune cells infiltrated than glioma patients with COPB2-low.…”

Section: Relationship Between Copb2 and Infiltrating Immune Cellsmentioning

confidence: 99%

High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma

et al. 2019

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Aims To evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis. Methods Oncomine, GEO, and The Cancer Genome Atlas databases were used to examine the COPB2 transcript levels in glioma tissues. Gene expression profiles with clinical information from low‐grade glioma and glioblastoma (GBM) projects were analyzed for associations between COPB2 expression and clinicopathologic characteristics. Kaplan‐Meier survival and Cox regression analyses were used for survival analysis. Gene set enrichment analysis (GSEA) was conducted to screen the pathways involved in COPB2 expression. Gene set variation analysis (GSVA) and correlograms were performed to verify the correlations between COPB2 and inflammatory responses. Canonical correlation analyses examined whether COPB2‐high patients have more infiltrating inflammatory and immune cells. Results COPB2 was highly expressed in gliomas and high COPB2 expression correlated with shorter overall survival time and several poor clinical prognostic variables. GSEA indicated that some immune‐related pathways and other signaling pathways in cancer were associated with the COPB2‐high phenotype. The GSVA and canonical correlation analysis demonstrated that COPB2 expression was closely linked to inflammatory and immune responses, and higher immune cell infiltration. Conclusions COPB2 may be a potential prognostic biomarker and an immunotherapeutic target for glioma.

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“…TGF-β1 belongs to a regulatory cytokine family with pleiotropic functions in many cell type lineages and is a critical differentiation factor for the generation of Treg cells. This cytokine can also induce the production of IL‑10 by Treg cells [23, 34, 35]. Moreover, a recent study showed that TGF-β1 can suppress autoreactive T cells independent of Treg cells [36].…”

Section: Discussionmentioning

confidence: 99%

Cytokines and Tissue Damage Biomarkers in First-Onset Neuromyelitis Optica Spectrum Disorders: Significance of Interleukin-6

Wei

Chang

et al. 2018

Neuroimmunomodulation

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Objective: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. Methods: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy. Fifteen patients with other noninflammatory neurological diseases (OND) were also included. The serum and CSF levels of interleukin (IL)-6, IL-10, IL-17, IL-21, IL-23, transforming growth factor (TGF)-β1 and the CSF levels of 3 biomarkers of axonal loss and astrocytic damage were measured using the human cytokine multiplex assay or ELISA. Results: Serum levels of IL-10 and TGF-β1 and CSF levels of IL-6, IL-10, and TGF-β1 were significantly increased in first-onset NMOSD compared to in OND patients. In a subgroup analysis, the CSF levels of IL-6, neurofilament light protein (NFL), S100B, and glial fibrillary acidic protein (GFAP) were significantly more elevated in the AQP4-IgG-positive patients than in the AQP4-IgG-negative NMOSD patients. Correlations were found between the CSF cytokines and tissue damage biomarkers and the clinical findings in NMOSD patients. Notably, the CSF IL-6 level had the strongest correlation with the tissue damage biomarkers and it also correlated with CSF white blood cell (WBC) count. Conclusions: IL-6 plays a role in the pathogenetic process of NMOSD, especially in the AQP4-IgG-positive subtype. Distinct pathogenesis exists between AQP4-IgG-positive and AQP4-IgG-negative NMOSD in the initial phase of the disease.

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TGF‐β Control of Adaptive Immune Tolerance: A Break From Treg Cells

Cited by 66 publications

References 56 publications

Exosomes of pasteurized milk: potential pathogens of Western diseases

Exosomes of pasteurized milk: potential pathogens of Western diseases

High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma

Cytokines and Tissue Damage Biomarkers in First-Onset Neuromyelitis Optica Spectrum Disorders: Significance of Interleukin-6

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