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Foxp3 epigenetics

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https://www.readbyqxmd.com/read/28736280/the-serine-threonine-protein-phosphatase-2a-controls-autoimmunity
#1
Amir Sharabi, Isaac R Kasper, George C Tsokos
Protein phosphatase 2A (PP2A) is the first Ser/Thr phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. B regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients...
July 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28709726/induction-and-maintenance-of-regulatory-t-cells-by-transcription-factors-and-epigenetic-modifications
#2
REVIEW
Mana Iizuka-Koga, Hiroko Nakatsukasa, Minako Ito, Takashi Akanuma, Qianjin Lu, Akihiko Yoshimura
Regulatory T cells (Tregs) are an essential cell subset for the maintenance of immune homeostasis. Foxp3 (Forkhead box P3) is the Treg master gene which is essential for immune suppressing activity. In addition, Tregs are characterized by a distinct pattern of gene expression, including upregulation of immune-suppressive genes and silencing of inflammatory genes. The molecular mechanisms of Treg development and maintenance have been intensively investigated. Tregs are characterized by expression of the transcription factor Foxp3...
July 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28702031/alloantigen-induced-regulatory-t-cells-generated-in-presence-of-vitamin-c-display-enhanced-stability-of-foxp3-expression-and-promote-skin-allograft-acceptance
#3
Eirini Nikolouli, Matthias Hardtke-Wolenski, Martin Hapke, Michael Beckstette, Robert Geffers, Stefan Floess, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are critical for the maintenance of immune homeostasis and self-tolerance and can be therapeutically used for prevention of unwanted immune responses such as allotransplant rejection. Tregs are characterized by expression of the transcription factor Foxp3, and recent work suggests that epigenetic imprinting of Foxp3 and other Treg-specific epigenetic signatures genes is crucial for the stabilization of both Foxp3 expression and immunosuppressive properties within Tregs. Lately, vitamin C was reported to enhance the activity of enzymes of the ten-eleven translocation family, thereby fostering the demethylation of Foxp3 and other Treg-specific epigenetic signatures genes in developing Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28693431/the-attenuation-of-renal-fibrosis-by-histone-deacetylase-inhibitors-is-associated-with-the-plasticity-of-foxp3-il-17-t-cells
#4
Wen-Pyng Wu, Yi-Giien Tsai, Tze-Yi Lin, Ming-Ju Wu, Ching-Yuang Lin
BACKGROUND: The histone deacetylase (HDAC) inhibitor, which has potential effects on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4(+) forkhead box P3 (FOXP3)(+) T regulatory (Treg) cells may be converted to inflammation-associated T helper 17 cells (Th17) with tissue fibrosis properties. The association between FOXP3(+)IL-17(+) T cells and the attenuation of renal fibrosis by the HDAC inhibitor is not clear. METHODS: This study evaluated the roles of the HDAC inhibitor, Treg cells and their differentiation into Th17 cells, which aggravate chronic inflammation and renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model...
July 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28543436/prenatal-environmental-tobacco-smoke-exposure-increases-allergic-asthma-risk-with-methylation-changes-in-mice
#5
Sonja Christensen, Zeina Jaffar, Elizabeth Cole, Virginia Porter, Maria Ferrini, Britten Postma, Kent E Pinkerton, Mihi Yang, Yang Jee Kim, Luke Montrose, Kevan Roberts, Andrij Holian, Yoon Hee Cho
Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6-7 weeks old to induce allergic inflammation...
July 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28522286/increased-proportions-of-functionally-impaired-regulatory-t-cell-subsets-in-systemic-sclerosis
#6
Emese Ugor, Diána Simon, Giovanni Almanzar, Ramóna Pap, József Najbauer, Péter Németh, Péter Balogh, Martina Prelog, László Czirják, Tímea Berki
Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis...
May 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#7
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#8
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28487700/l-arginine-dependent-epigenetic-regulation-of-interleukin-10-but-not-transforming-growth-factor-%C3%AE-production-by-neonatal-regulatory-t-lymphocytes
#9
Hong-Ren Yu, Ching-Chang Tsai, Ling-Sai Chang, Hsin-Chun Huang, Hsin-Hsin Cheng, Jiu-Yao Wang, Jiunn-Ming Sheen, Ho-Chang Kuo, Kai-Sheng Hsieh, Ying-Hsien Huang, Kuender D Yang, Te-Yao Hsu
A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28477096/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-i-origin-phenotype-mechanisms
#10
REVIEW
Katarzyna Bocian, Ewelina Kiernozek, Joanna Domagała-Kulawik, Grażyna Korczak-Kowalska, Anna Stelmaszczyk-Emmel, Nadzieja Drela
Immunosuppressive activity of regulatory T and B cells is critical to limit autoimmunity, excessive inflammation, and pathological immune response to conventional antigens or allergens. Both types of regulatory cells are intensively investigated, however, their development and mechanisms of action are still not completely understood. Both T and B regulatory cells represent highly differentiated populations in terms of phenotypes and origin, however, they use similar mechanisms of action. The most investigated CD4(+)CD25(+) regulatory T cells are characterized by the expression of Foxp3(+) transcription factor, which is not sufficient to maintain their lineage stability and suppressive function...
May 5, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28454014/reduced-mouse-allergen-is-associated-with-epigenetic-changes-in-regulatory-genes-but-not-mouse-sensitization-in-asthmatic-children
#11
RANDOMIZED CONTROLLED TRIAL
Rachel L Miller, Hanjie Zhang, Jacqueline Jezioro, Mariangels De Planell Saguer, Stephanie Lovinsky-Desir, Xinhua Liu, Matthew Perzanowski, Adnan Divjan, Wanda Phipatanakul, Elizabeth C Matsui
Chronic exposure to mouse allergen may contribute greatly to the inner-city asthma burden. We hypothesized that reducing mouse allergen exposure may modulate the immunopathology underlying symptomatic pediatric allergic asthma, and that this occurs through epigenetic regulation. To test this hypothesis, we studied a cohort of mouse sensitized, persistent asthmatic inner-city children undergoing mouse allergen-targeted integrated pest management (IPM) vs education in a randomized controlled intervention trial...
July 2017: Environmental Research
https://www.readbyqxmd.com/read/28415767/unique-properties-of-thymic-antigen-presenting-cells-promote-epigenetic-imprinting-of-alloantigen-specific-regulatory-t-cells
#12
Garima Garg, Eirini Nikolouli, Matthias Hardtke-Wolenski, Aras Toker, Naganari Ohkura, Michael Beckstette, Takahisa Miyao, Robert Geffers, Stefan Floess, Norbert Gerdes, Esther Lutgens, Anke Osterloh, Shohei Hori, Shimon Sakaguchi, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce transplantation tolerance. However, stability of Tregs still remains contentious and may potentially restrict their clinical use. Recent work suggested that epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these events are initiated already during early stages of thymic Treg development. However, the mechanisms governing this process remain largely unknown...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#13
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28397379/b-fahf-2-plus-oral-immunotherapy-oit-is-safer-and-more-effective-than-oit-alone-in-a-murine-model-of-concurrent-peanut-tree-nut-allergy
#14
Kamal D Srivastava, Ying Song, Nan Yang, Changda Liu, Ilan E Goldberg, Anna Nowak-Węgrzyn, Hugh A Sampson, Xiu-Min Li
BACKGROUND: Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory. OBJECTIVE: To determine if the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state. METHODS: Concurrently sensitized peanut, walnut (WN) and cashew (CSH) allergic mice received 1 day PN/WN/CSH rush OIT plus 3 weeks of maintenance dosing, with or without 3-weeks prior and 3-weeks BF2 co-treatment...
April 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28396406/flicr-a-long-noncoding-rna-modulates-foxp3-expression-and-autoimmunity
#15
David Zemmour, Alvin Pratama, Scott M Loughhead, Diane Mathis, Christophe Benoist
A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in a subset of Tregs with twofold- to fivefold-lower levels of FoxP3 protein. The impact of Flicr is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses Flicr expression...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28387568/non-linear-patterns-in-age-related-dna-methylation-may-reflect-cd4-t-cell-differentiation
#16
Nicholas D Johnson, Howard W Wiener, Alicia K Smith, Shota Nishitani, Devin M Absher, Donna K Arnett, Stella Aslibekyan, Karen N Conneely
DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1...
June 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28362657/epigenetics-of-cd4-t-cells-in-autoimmune-diseases
#17
Zijun Wang, Christopher Chang, Qianjin Lu
PURPOSE OF REVIEW: Autoimmune disorders are a group of overactive symptoms because of abnormal immune responses. Progress of novel mechanisms for autoimmune diseases has been restrained by incomplete understanding of immune disturbance. Recent advances in autoimmune diseases have been well documented by epigenetic alterations (DNA methylation, histone modification, and microRNAs), which alter the transcription activity of genes that are involved in autoimmune responses. RECENT FINDINGS: Multiple environmental factors (trichloroethylene, breast milk, and vitamin C) initiate aberrant epigenetic modifications in CD4 T cells, leading to a list of transcriptional deregulations in several genes (Ifng, Cd70, Tnf, Dnmt3a, and Foxp3) that determine T-cell identity...
July 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#18
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28320913/relationship-between-cd4-regulatory-t-cells-and-anergy-in-vivo
#19
REVIEW
Lokesh A Kalekar, Daniel L Mueller
Selective suppression of effector CD4(+) T cell functions is necessary to prevent immune cell-mediated damage to healthy tissues. This appears especially true during pregnancy or in individuals predisposed to autoimmunity. Foxp3(+) regulatory T (Treg) cells and induction of anergy, an acquired state of T cell functional unresponsiveness in Foxp3(-) cells, have both been implicated as mechanisms to suppress dangerous immune responses to tissue-restricted self-Ags. Anergic CD4(+) T cells and Treg cells share a number of phenotypic and mechanistic traits-including the expression of CD73 and folate receptor 4, and the epigenetic modification of Treg cell signature genes-and an interesting relationship between these two subsets has recently emerged...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#20
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
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