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Foxp3 gene

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https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#1
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#2
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902985/disease-manifestation-and-inflammatory-activity-as-modulators-of-th17-treg-balance-and-rorc-foxp3-methylation-in-systemic-sclerosis
#3
Giovanni Almanzar, Matthias Klein, Marc Schmalzing, Deborah Hilligardt, Nady El Hajj, Hermann Kneitz, Vanessa Wild, Andreas Rosenwald, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Thomas Haaf, Matthias Goebeler, Martina Prelog
BACKGROUND: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. METHODS: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27901054/functional-defects-in-cd4-cd25-high-foxp3-regulatory-cells-in-ankylosing-spondylitis
#4
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/27893200/clinical-impact-of-overexpression-of-foxp3-and-wt1-on-disease-outcome-in-egyptian-acute-myeloid-leukemia-patients
#5
Magda Assem, Ahmed Osman, Eman Kandeel, Reham Elshimy, Hanan Nassar, Radwa Ali
Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric)...
January 10, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27892628/association-between-foxp3-gene-polymorphisms-and-risk-of-differentiated-thyroid-cancer-in-chinese-han-population
#6
Weichao Jiang, Lei Zheng, Lijuan Xu, Yang Zhang, Xingxin Liu, Lihua Hu, Xiaobei Wang
BACKGROUND: Foxp3 plays important roles in autoimmune and inflammatory diseases as well as human malignancies. This study aimed to investigate the association between Foxp3 gene polymorphisms and the susceptibility to differentiated thyroid cancers (DTC). METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 350 DTC patients and 306 healthy controls. FOXP3 relative expression was measured by real-time quantitative PCR (qRT-PCR)...
November 28, 2016: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/27887954/the-short-chain-fatty-acid-sodium-butyrate-functions-as-a-regulator-of-the-skin-immune-system
#7
Agatha Schwarz, Anika Bruhs, Thomas Schwarz
There is evidence that gut commensal microbes affect the mucosal immune system via expansion of regulatory T cells (Treg) in the colon. This is mediated via short-chain fatty acids (SCFA), bacterial metabolites generated during fiber fermentation, which include butyrate, propionate and acetate. We postulated that SCFA produced by commensal skin bacteria may also activate resident skin Treg, the activity of which is diminished in certain inflammatory dermatoses. Sodium butyrate (SB) either injected s.c. or applied topically onto the ears of hapten-sensitized mice significantly reduced the contact hypersensitivity reaction...
November 22, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27885422/cd44-induces-foxp3-expression-and-is-related-with-favorable-outcome-in-breast-carcinoma
#8
Elena Sanmartín, Fernando Ortiz-Martínez, Eloy Pomares-Navarro, Araceli García-Martínez, Montserrat Rodrigo-Baños, Marta García-Escolano, Leire Andrés, Enrique Lerma, Francisco I Aranda, Pascual Martínez-Peinado, José M Sempere-Ortells, Gloria Peiró
We studied the relationship between CD44 and Forkhead box P3 (FOXP3) gene expression in cell lines and breast carcinomas and their association with clinicopathological variables and patient outcome. We assessed messenger RNA (mRNA) expression of CD44 and FOXP3 by quantitative real-time PCR and determined the number of FOXP3+ Tregs by immunohistochemistry in 264 breast cancer specimens. CD44 was stimulated with hyaluronan treatment, and the accompanying changes in FOXP3 mRNA expression in breast cancer cell lines representing breast cancer subtype were assessed...
November 24, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27884791/immunomodulatory-effect-of-characterized-extract-of-zataria-multiflora-on-th1-th2-and-th17-in-normal-and-th2-polarization-state
#9
Majid Kianmehr, Abdolrahim Rezaei, Mahmoud Hosseini, Mohammad Reza Khazdair, Ramin Rezaee, Vahid Reza Askari, Mohammad Hossein Boskabady
The effect of the extract of Zataria multiflora (Z. multiflora) on IFN-γ, FOXP3, IL-4, TGF-β, and IL-17 gene expression was evaluated in cultured splenocytes obtained from control, nontreated asthma or sensitized mice (group S), Sensetized animals treated with dexamethasone or three concentrations of Z. multiflora extract (200, 400 and 800 μg/ml) (n = 6, for each group). IFN-γ and FOXP3 gene expressions were significantly decreased (P < 0.001 for both cases) but IL-4 (P < 0.001) and IL-17 (P < 0...
November 21, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27878451/beyond-genetics-what-causes-type-1-diabetes
#10
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/27878248/immunomodulatory-effects-of-ox40ig-gene-modified-adipose-tissue-derived-mesenchymal-stem-cells-on-rat-kidney-transplantation
#11
Tao Liu, Yue Zhang, Zhongyang Shen, Xunfeng Zou, Xiaobo Chen, Li Chen, Yuliang Wang
Recent studies have suggested that adipose tissue-derived mesenchymal stem cell (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory strategies used to suppress the immune response to alloantigens. However, relatively little has been reported regarding the immunomodulatory potential of the abilityof these two strategies to synergize. Thus, in the present study, we aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to validate their more potent immunosuppressive activity in preventing renal allograft rejection...
November 21, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#12
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/27868139/clinical-genetic-and-innate-immunity-characteristics-of-melanoma-in-organ-transplant-recipients
#13
Anabelle Brocard, Anne-Chantal Knol, Céline Bossard, Marc G Denis, Gaëlle Quéreux, Mélanie Saint-Jean, Lucie Peuvrel, Amir Khammari, Gilles Blancho, Jacques Dantal, Brigitte Dréno
The aims of this study were to determine the clinical and histological characteristics of melanoma in transplant recipients, the mutation profile (BRAF, NRAS and c-KIT genes), and the immune tolerance of the tumour microenvironment by immunohistochemical study of the expression of IDO, PD1, PD-L1, CD8 and FoxP3. The study population comprised patients who had undergone a renal transplant in Nantes University Hospital who developed post-transplantation melanoma. Twenty cases of melanoma out of 4,663 transplant recipients were studied...
November 10, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27865612/changes-in-intestinal-immunity-gut-microbiota-and-expression-of-energy-metabolism-related-genes-explain-adenoma-growth-in-bilberry-and-cloudberry-fed-apc-min-mice
#14
Essi Päivärinta, Mikael Niku, Johanna Maukonen, Markus Storvik, Anu Heiman-Lindh, Maria Saarela, Anne-Maria Pajari, Marja Mutanen
We showed previously that ellagitannin-rich cloudberries and anthocyanin-rich bilberries reduce the number of intestinal adenomas in multiple intestinal neoplasia/+ (Apc(Min)) mice. We also found that cloudberries decreased the size of adenomas, whereas bilberries increased it. Here we hypothesized that the difference in adenoma growth could be explained by dissimilar effects of the berries on intestinal immune responses and gut microbiota, potentially driven by the distinct polyphenol compositions of the 2 berries...
October 15, 2016: Nutrition Research
https://www.readbyqxmd.com/read/27859672/immune-activation-and-regulation-related-patterns-in-stable-hand-transplant-recipients
#15
Dorota Kamińska, Katarzyna Kościelska-Kasprzak, Magdalena Krajewska, Adam Chełmoński, Jerzy Jabłecki, Marcelina Żabińska, Marta Myszka, Mirosław Banasik, Maria Boratyńska, Agnieszka Gomółkiewicz, Piotr Dzięgiel, Marian Klinger
BACKGROUND: We assessed cell subsets and expression of a set of genes related to the T cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). MATERIAL AND METHODS: The study was conducted on 5 HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, TNFA genes on a custom designed low density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations...
November 9, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27857073/usp21-prevents-the-generation-of-t-helper-1-like-treg-cells
#16
Yangyang Li, Yue Lu, Shuaiwei Wang, Zhijun Han, Fuxiang Zhu, Yingmeng Ni, Rui Liang, Yan Zhang, Qibin Leng, Gang Wei, Guochao Shi, Ruihong Zhu, Dan Li, Haikun Wang, Song Guo Zheng, Hongxi Xu, Andy Tsun, Bin Li
FOXP3(+) Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells...
November 18, 2016: Nature Communications
https://www.readbyqxmd.com/read/27851926/local-cellular-and-cytokine-cues-in-the-spleen-regulate-in-situ-t-cell-receptor-affinity-function-and-fate-of-cd8-t-cells
#17
Young-Jin Seo, Prithiviraj Jothikumar, Mehul S Suthar, Cheng Zhu, Arash Grakoui
T cells rapidly undergo contraction upon viral clearance, but how T cell function and fate are determined during this phase is unclear. During the contraction phase of an acute infection with lymphocytic choriomeningitis virus, we found that virus-specific CD8(+) T cells within the splenic red pulp (RP) had higher two-dimensional (2D) effective affinity than those within the white pulp (WP). This increased antigen recognition of RP-derived CD8(+) T cells correlated with more efficient target cell killing and improved control of viremia...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27843539/regulatory-and-activated-effector-t-cells-in-chronic-hepatitis-c-virus-relation-to-autoimmunity
#18
Hanan Fouad, Maissa El Raziky, Eman Medhat Hassan, Ghada Mahmoud Abdel Aziz, Samar K Darweesh, Ahmed Reda Sayed
AIM: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS: A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group...
October 28, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27833053/western-diet-enhances-intestinal-tumorigenesis-in-min-mice-associating-with-mucosal-metabolic-and-inflammatory-stress-and-loss-of-apc-heterozygosity
#19
Mikael Niku, Anne-Maria Pajari, Laura Sarantaus, Essi Päivärinta, Markus Storvik, Anu Heiman-Lindh, Santeri Suokas, Minna Nyström, Marja Mutanen
Western-type diet (WD) is a risk factor for colorectal cancer, but the underlying mechanisms are poorly understood. We investigated the interaction of WD and heterozygous mutation in the Apc gene on adenoma formation and metabolic and immunological changes in the histologically normal intestinal mucosa of Apc(Min/+) (Min/+) mice. The diet used was high in saturated fat and low in calcium, vitamin D, fiber and folate. The number of adenomas was twofold higher in the WD mice compared to controls, but adenoma size, proliferation or apoptosis did not differ...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27830498/wilms-tumor-susceptibility-possible-involvement-of-foxp3-and-cxcl12-genes
#20
Patricia Midori Murobushi Ozawa, Carolina Batista Ariza, Roberta Losi-Guembarovski, Alda Losi Guembarovski, Carlos Eduardo Coral de Oliveira, Bruna Karina Banin-Hirata, Marina Okuyama Kishima, Diego Lima Petenuci, Maria Angelica Ehara Watanabe
BACKGROUND: Wilms' tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance...
December 2016: Molecular and Cellular Pediatrics
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