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Foxp3 epigenetics

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https://www.readbyqxmd.com/read/28228556/activation-and-functional-specialization-of-regulatory-t-cells-lead-to-the-generation-of-foxp3-instability
#1
Zhongmei Zhang, Wei Zhang, Jie Guo, Qianchong Gu, Xueping Zhu, Xuyu Zhou
Accumulating evidence suggests that Foxp3(+) cells can downregulate the expression of Foxp3, but whether thymically derived regulatory T cells (tTregs; especially committed tTregs) are capable of downregulating Foxp3 expression and being reprogrammed into other T effector cells remains controversial. Using a novel tTreg lineage-tracing mouse line, we were able to label epigenetically stable Foxp3(+) cells derived from the thymus and demonstrate that mature tTregs are stable under homeostatic conditions. However, TCR engagement and sequential functional specialization of tTregs led to the generation of Foxp3 instability and reprogramming into the Th lineage...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28194445/diverse-repetitive-element-rna-expression-defines-epigenetic-and-immunologic-features-of-colon-cancer
#2
Niyati Desai, Dipti Sajed, Kshitij S Arora, Alexander Solovyov, Mihir Rajurkar, Jacob R Bledsoe, Srinjoy Sil, Ramzi Amri, Eric Tai, Olivia C MacKenzie, Mari Mino-Kenudson, Martin J Aryee, Cristina R Ferrone, David L Berger, Miguel N Rivera, Benjamin D Greenbaum, Vikram Deshpande, David T Ting
There is tremendous excitement for the potential of epigenetic therapies in cancer, but the ability to predict and monitor response to these drugs remains elusive. This is in part due to the inability to differentiate the direct cytotoxic and the immunomodulatory effects of these drugs. The DNA-hypomethylating agent 5-azacitidine (AZA) has shown these distinct effects in colon cancer and appears to be linked to the derepression of repeat RNAs. LINE and HERV are two of the largest classes of repeats in the genome, and despite many commonalities, we found that there is heterogeneity in behavior among repeat subtypes...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28102058/neonatal-immune-state-is-influenced-by-maternal-allergic-rhinitis-and-associated-with-regulatory-t-cells
#3
Lu Tan, Jing Ou, Zezhang Tao, Yonggang Kong, Yu Xu
PURPOSE: Maternal influences contribute to the origin of allergic diseases, but the mechanisms are not clear. The current literature prompted the role of epigenetics in the development of allergic diseases. We sought to investigate the roles of regulatory T (Treg) cells and Forkhead box p3 (Foxp3) DNA methylation in the process of maternal transmission of allergic rhinitis (AR) susceptibility. METHODS: BALB/c female mice (AR mother) were sensitized by intraperitoneal injection of Dermatophagoides pteronyssinus (Der p) 1 on day 1 and 7...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28100624/azacytidine-treatment-inhibits-the-progression-of-herpes-stromal-keratitis-by-enhancing-regulatory-t-cell-function
#4
Siva Karthik Varanasi, Pradeep B J Reddy, Siddheshvar Bhela, Ujjaldeep Jaggi, Fernanda Gimenez, Barry T Rouse
: Ocular infection with Herpes Simplex Virus type 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance as well as chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit Stromal Keratitis (SK) lesion severity. In this report, we have explored the novel approach of inhibiting DNA methyltransferase activity using 5-Azacytidine (cytosine analog) to limit HSV-1 induced ocular lesions...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#5
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
: Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the FOXP3 Treg-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27936497/proinflammatory-cytokine-interferon-%C3%AE-and-microbiome-derived-metabolites-dictate-epigenetic-switch-between-forkhead-box-protein-3-isoforms-in-coeliac-disease
#6
G Serena, S Yan, S Camhi, S Patel, R S Lima, A Sapone, M M Leonard, R Mukherjee, B J Nath, K M Lammers, A Fasano
Coeliac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong T helper type 1 (Th1)/Th17 immune response in the small intestine. Regulatory T cells (Treg ) are CD4(+) CD25(++) forkhead box protein 3 (FoxP3(+) ) cells that regulate the immune response. Conversely to its counterpart, FoxP3 full length (FL), the alternatively spliced isoform FoxP3 Δ2, cannot properly down-regulate the Th17-driven immune response. As the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FoxP3 isoforms may be associated with the disease...
March 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27901054/functional-defects-in-cd4-cd25-high-foxp3-regulatory-cells-in-ankylosing-spondylitis
#7
Huifang Guo, Ming Zheng, Kui Zhang, Fengfan Yang, Xin Zhang, Qing Han, Zhi-Nan Chen, Ping Zhu
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how Tregs participate in the pathogenesis of ankylosing spondylitis (AS) has not been fully elucidated. Here, we investigated Treg function and found that Tregs in peripheral blood (PB) from patients with active AS had lower FoxP3 mean fluorescence intensity (MFI) than those from healthy controls and could not fully suppress naïve T cell (Tn) proliferation...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27878451/beyond-genetics-what-causes-type-1-diabetes
#8
REVIEW
Zhen Wang, Zhiguo Xie, Qianjin Lu, Christopher Chang, Zhiguang Zhou
Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated β cell destruction in the pancreas of genetically susceptible individuals. Extensive familial and population genetic studies uncovered the strong linkage and association between HLA gene variants and T1D. Non-HLA genes have also been associated with T1D, such as INS, CTLA4, and PTPN22. T1D is considered as one of the most heritable common diseases. However, evidence that monozygotic twins have incomplete concordance of disease susceptibility provides convincing proof that environmental factors also play important roles in the pathogenesis of the disease...
November 22, 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#9
Chun-Hao Lu, Cheng-Jang Wu, Cheng-Chi Chan, Duc T Nguyen, Kuo-Ray Lin, Syh-Jae Lin, Li-Chen Chen, Jeffrey Jong-Yong Yen, Ming-Ling Kuo
The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4(+) regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4(+)CD25(h)FOXP3(+) T cell induction from human CD4(+)CD25(-) T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27799308/bptf-is-essential-for-t-cell-homeostasis-and-function
#10
Bing Wu, Yunqi Wang, Chaojun Wang, Gang Greg Wang, Jie Wu, Yisong Y Wan
Bromodomain PHD finger transcription factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. Although BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late double-negative 3/double-negative 4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell-intrinsic manner...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27778276/transcriptional-modulation-of-regulatory-t-cell-development-by-novel-regulators-nr4as
#11
REVIEW
Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
November 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27687891/epigenetic-variability-of-cd4-cd25-tregs-contributes-to-the-pathogenesis-of-autoimmune-diseases
#12
Ye Shu, Qinghua Hu, Hai Long, Christopher Chang, Qianjin Lu, Rong Xiao
Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues. However, the exact mechanisms underlying the development of these conditions remain unknown. CD4+CD25+ regulatory T cells (Tregs) are a subset of mature T cells which have an important role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box p3 (Foxp3), a member of the fork head transcription factor family, is recognized as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+ Tregs in peripheral blood and related tissues has been demonstrated in systemic lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are at least partially regulated by epigenetic mechanisms...
September 29, 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27659419/foxp3-promoter-methylation-impairs-suppressive-function-of-regulatory-t-cells-in-biliary-atresia
#13
Kang Li, Xi Zhang, Li Yang, Xin-Xing Wang, De-Hua Yang, Guo-Qing Cao, Shuai Li, Yong-Zhong Mao, Shao-Tao Tang
Biliary atresia (BA) is characterized by progressive inflammation of the biliary system leading to liver cirrhosis, necessitating liver transplantation in pediatric patients. Various cell types have been reported to participate in the proinflammatory response in rhesus rotavirus (RRV)-induced BA mouse models, including T helper (Th) 1, Th2, Th17, CD8(+) T cells, and natural killer cells. The immune suppressive regulatory T (Treg) cells, on the contrary, were reported not to function properly. The underlying mechanism is largely unknown...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27587669/luxglm-a-probabilistic-covariate-model-for-quantification-of-dna-methylation-modifications-with-complex-experimental-designs
#14
Tarmo Äijö, Xiaojing Yue, Anjana Rao, Harri Lähdesmäki
MOTIVATION: 5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood...
September 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27525046/epigenetic-features-of-foxp3-in-children-with-cow-s-milk-allergy
#15
Lorella Paparo, Rita Nocerino, Linda Cosenza, Rosita Aitoro, Valeria D'Argenio, Valentina Del Monaco, Carmen Di Scala, Antonio Amoroso, Margherita Di Costanzo, Francesco Salvatore, Roberto Berni Canani
BACKGROUND: DNA methylation of the Th1 and Th2 cytokine genes is altered during cow's milk allergy (CMA). Forkhead box transcription factor 3 (FoxP3) is essential for the development and function of regulatory T cells (Tregs) and is involved in oral tolerance acquisition. We assessed whether tolerance acquisition in children with IgE-mediated CMA is associated with DNA demethylation of the Treg-specific demethylated region (TSDR) of FoxP3. RESULTS: Forty children (aged 3-18 months) were enrolled: 10 children with active IgE-mediated CMA (group 1), 10 children who outgrew CMA after dietary treatment with an extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG (group 2), 10 children who outgrew CMA after treatment with other formulas (group 3), and 10 healthy controls (group 4)...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27499494/the-ratio-of-regulatory-foxp3-to-total-cd3-t-cells-determined-by-epigenetic-cell-counting-and-cardiovascular-disease-risk-a-prospective-case-cohort-study-in-non-diabetics
#16
Sebastian Dietmar Barth, Rudolf Kaaks, Theron Johnson, Verena Katzke, Katharina Gellhaus, Janika Josephin Schulze, Sven Olek, Tilman Kühn
BACKGROUND: Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disease incidence remains uncertain. METHODS: A nested case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random subcohort (n=778) and primary cases of myocardial infarction (MI, n=276) and ischemic stroke (n=151)...
September 2016: EBioMedicine
https://www.readbyqxmd.com/read/27314687/dna-methylation-a-new-player-in-multiple-sclerosis
#17
Xiang Li, Bing Xiao, Xing-Shu Chen
Multiple sclerosis (MS) is a neurological and chronic inflammatory disease that is mediated by demyelination and axonal degeneration in the central nervous system (CNS). Studies have shown that immune system components such as CD4+, CD8+, CD44+ T cells, B lymphatic cells, and inflammatory cytokines play a critical role in inflammatory processes and myelin damage associated with MS. Nevertheless, the pathogenesis of MS remains poorly defined. DNA methylation, a significant epigenetic modification, is reported to be extensively involved in MS pathogenesis through the regulation of gene expression...
June 17, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27175277/milk-a-postnatal-imprinting-system-stabilizing-foxp3-expression-and-regulatory-t-cell-differentiation
#18
REVIEW
Bodo C Melnik, Swen Malte John, Pedro Carrera-Bastos, Gerd Schmitz
BACKGROUND: Breastfeeding has protective effects for the development of allergies and atopy. Recent evidence underlines that consumption of unboiled farm milk in early life is a key factor preventing the development of atopic diseases. Farm milk intake has been associated with increased demethylation of FOXP3 and increased numbers of regulatory T cells (Tregs). Thus, the questions arose which components of farm milk control the differentiation and function of Tregs, critical T cell subsets that promote tolerance induction and inhibit the development of allergy and autoimmunity...
2016: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/27148253/induced-foxp3-t-cells-colonizing-tolerated-allografts-exhibit-the-hypomethylation-pattern-typical-of-mature-regulatory-t-cells
#19
Robert Hilbrands, Ye Chen, Adrian R Kendal, Elizabeth Adams, Stephen P Cobbold, Herman Waldmann, Duncan Howie
Regulatory T cells expressing the transcription factor Foxp3 require acquisition of a specific hypomethylation pattern to ensure optimal functional commitment, limited lineage plasticity, and long-term maintenance of tolerance. A better understanding of the molecular mechanisms involved in the generation of these epigenetic changes in vivo will contribute to the clinical exploitation of Foxp3(+) Treg. Here, we show that both in vitro and in vivo generated antigen-specific Foxp3(+) Treg can acquire Treg-specific epigenetic characteristics and prevent skin graft rejection in an animal model...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27078110/immuno-navigator-a-batch-corrected-coexpression-database-reveals-cell-type-specific-gene-networks-in-the-immune-system
#20
Alexis Vandenbon, Viet H Dinh, Norihisa Mikami, Yohko Kitagawa, Shunsuke Teraguchi, Naganari Ohkura, Shimon Sakaguchi
High-throughput gene expression data are one of the primary resources for exploring complex intracellular dynamics in modern biology. The integration of large amounts of public data may allow us to examine general dynamical relationships between regulators and target genes. However, obstacles for such analyses are study-specific biases or batch effects in the original data. Here we present Immuno-Navigator, a batch-corrected gene expression and coexpression database for 24 cell types of the mouse immune system...
April 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
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