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Foxp3 epigenetics

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https://www.readbyqxmd.com/read/27936497/pro-inflammatory-cytokine-ifn%C3%AE-and-microbiome-derived-metabolites-dictate-epigenetic-switch-between-foxp3-isoforms-in-celiac-disease-regulation-of-foxp3-isoforms-in-celiac-disease
#1
Gloria Serena, Shu Yan, Stephanie Camhi, Shilpi Patel, Rosiane S Lima, Anna Sapone, Maureen M Leonard, Rupa Mukherjee, Barbara J Nath, Karen M Lammers, Alessio Fasano
Celiac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong Th1/Th17 immune response in the small intestine. Treg cells are CD4(+) CD25(++) 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 Th17 driven immune response. Since 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...
December 9, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27901054/functional-defects-in-cd4-cd25-high-foxp3-regulatory-cells-in-ankylosing-spondylitis
#2
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
#3
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
#4
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
#5
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
#6
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...
October 25, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27687891/epigenetic-variability-of-cd4-cd25-tregs-contributes-to-the-pathogenesis-of-autoimmune-diseases
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27044095/nuclear-transfer-ntreg-model-reveals-fate-determining-tcr-%C3%AE-and-novel-peripheral-ntreg-precursors
#16
Manching Ku, Shih-En Chang, Julio Hernandez, Justin R Abadejos, Mohsen Sabouri-Ghomi, Niklas J Muenchmeier, Anna Schwarz, Anna M Valencia, Oktay Kirak
To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3(+)CD4(+)Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) β-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR β-chain was able to provide stronger TCR signals...
April 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26999211/different-subsets-of-t-cells-memory-effector-functions-and-car-t-immunotherapy
#17
REVIEW
Vita Golubovskaya, Lijun Wu
This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc...
2016: Cancers
https://www.readbyqxmd.com/read/26849732/o-015%C3%A2-yi%C3%A2-alterations-in-the-foxp3-ezh2-pathway-associates-with-increased-susceptibility-to-colitis-in-both-mice-and-human
#18
Olga Sarmento, Yuning Xiong, Zhifu Sun, Phyllis Svingen, Adebowale Bamidele, Thomas Smyrk, Asha Nair, Saurabh Baheti, Dermot McGovern, Jessica Friton, Konstantinos Papadakis, Gautam Goel, Ramnik Xavier, Raul Urrutia, William Faubion
BACKGROUND: Crohn's disease is a common intestinal inflammatory disorder of uncertain etiology and incomplete treatment options. It is characterized by lesions infiltrated by inflammatory CD4 lymphocytes; yet the mechanism of CD4 mediated pathophysiology is unclear. Through whole genome approaches on clinical cohorts of CD patients, combined with functional in-vivo and in-vitro murine data, we sought to identify and evaluate aberrant transcriptional gene networks in disease-associated CD4 cells...
March 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/26774863/t-reg-stability-to-be-or-not-to-be
#19
REVIEW
Abigail E Overacre, Dario Aa Vignali
Regulatory T cell (T(reg)) stability has been primarily determined by the maintained expression of the transcription factor Forkhead box P3 (Foxp3). However, T(regs) can exhibit instability while maintaining Foxp3 expression, requiring a re-examination of what defines T(reg) stability. Recent work suggests that the establishment and stability of T(regs) is mediated by a number of mechanisms besides Foxp3 expression, such as epigenetic modifications, Foxo1/3a localization, expression of Eos and signaling via Neuropilin-1...
April 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/26768846/unstable-foxp3-t-regulatory-cells-in-nzw-mice
#20
Fabien Dépis, Ho-Keun Kwon, Diane Mathis, Christophe Benoist
Regulatory T (Treg) cells that express the transcription factor FoxP3 play a key role in self-tolerance and the control of inflammation. In mice and humans, there is a wide interindividual range in Treg frequency, but little is known about the underlying genetic or epigenetic mechanisms. We explored this issue in inbred strains of mice, with a special focus on the low proportion of Treg cells found in NZW mice. Mixed bone marrow chimera experiments showed this paucity to be intrinsic to NZW Treg cells, a dearth that could be tied to poor stability of the Treg pool and of FoxP3 expression...
February 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
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