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https://www.readbyqxmd.com/read/29456534/critical-role-of-tgf-%C3%AE-and-il-2-receptor-signaling-in-foxp3-induction-by-an-inhibitor-of-dna-methylation
#1
Kristin Freudenberg, Nadja Lindner, Sebastian Dohnke, Annette I Garbe, Sonja Schallenberg, Karsten Kretschmer
Under physiological conditions, CD4+ regulatory T (Treg) cells expressing the transcription factor Foxp3 are generated in the thymus [thymus-derived Foxp3+ Treg (tTregs) cells] and extrathymically at peripheral sites [peripherally induced Foxp3+ Treg (pTreg) cell], and both developmental subsets play non-redundant roles in maintaining self-tolerance throughout life. In addition, a variety of experimental in vitro and in vivo modalities can extrathymically elicit a Foxp3+ Treg cell phenotype in peripheral CD4+ Foxp3- T cells, which has attracted much interest as an approach toward cell-based therapy in clinical settings of undesired immune responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29414937/c-maf-dependent-regulatory-t-cells-mediate-immunological-tolerance-to-a-gut-pathobiont
#2
Mo Xu, Maria Pokrovskii, Yi Ding, Ren Yi, Christy Au, Oliver J Harrison, Carolina Galan, Yasmine Belkaid, Richard Bonneau, Dan R Littman
Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt+FOXP3+ regulatory T (iTreg) cells that selectively restrain pro-inflammatory T helper 17 (TH17) cells and whose function is dependent on the transcription factor c-MAF...
February 7, 2018: Nature
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#3
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29387988/using-marker-gene-analysis-instead-of-mixed-lymphocyte-reaction-assay-for-identification-of-functional-cd4-foxp3-regulatory-t-cells
#4
Sin-Tak Chu, Kuo-Hsuan Chien, Hsiu-Hsia Lin, Wei-Hao Wu, Jhih-Yun Jian, Woan-Fang Tzeng, Tzeon-Jye Chiou
OBJECTIVE: To establish a quick analytical method using quantitative PCR for marker gene analysis to identify the functions of iTreg cells and subsequently curtail the harvest time for iTreg cells. RESULTS: The data from the marker gene analysis indicated that varying proportions of iTreg cells could reveal the various expression levels of these genes. FoxP3 expression increased to a considerable degree. By using the same iTreg population, the mixed lymphocyte reaction assay was conducted for 5 days...
January 31, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29386580/il-6-receptor-blockade-corrects-defects-of-xiap-deficient-regulatory-t-cells
#5
Wan-Chen Hsieh, Tzu-Sheng Hsu, Ya-Jen Chang, Ming-Zong Lai
X-linked lymphoproliferative syndrome type-2 (XLP-2) is a primary immunodeficiency disease attributed to XIAP mutation and is triggered by infection. Here, we show that mouse Xiap -/- regulatory T (Treg) cells and human XIAP-deficient Treg cells are defective in suppressive function. The Xiap -/- Treg cell defect is linked partly to decreased SOCS1 expression. XIAP binds SOCS1 and promotes SOCS1 stabilization. Foxp3 stability is reduced in Xiap -/- Treg cells. In addition, Xiap -/- Treg cells are prone to IFN-γ secretion...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29382747/targeting-jak2-reduces-gvhd-and-xenograft-rejection-through-regulation-of-t-cell-differentiation
#6
Brian C Betts, David Bastian, Supinya Iamsawat, Hung Nguyen, Jessica L Heinrichs, Yongxia Wu, Anusara Daenthanasanmak, Anandharaman Veerapathran, Alison O'Mahony, Kelly Walton, Jordan Reff, Pedro Horna, Elizabeth M Sagatys, Marie C Lee, Jack Singer, Ying-Jun Chang, Chen Liu, Joseph Pidala, Claudio Anasetti, Xue-Zhong Yu
Janus kinase 2 (JAK2) signal transduction is a critical mediator of the immune response. JAK2 is implicated in the onset of graft-versus-host disease (GVHD), which is a significant cause of transplant-related mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Transfer of JAK2-/- donor T cells to allogeneic recipients leads to attenuated GVHD yet maintains graft-versus-leukemia. Th1 differentiation among JAK2-/- T cells is significantly decreased compared with wild-type controls. Conversely, iTreg and Th2 polarization is significantly increased among JAK2-/- T cells...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29370826/bank1-alters-b-cell-responses-and-influences-the-interactions-between-b-cells-and-induced-t-regulatory-cells-in-mice-with-collagen-induced-arthritis
#7
Jie Yang, Jie Ren, Yiming Yang, Juan Sun, Xiaohui Zhou, Shucong Zheng, Dandan Xuan, Yu Xue, Huimin Fan, Jiong Zhang, Hejian Zou, Weiguo Wan, Ning Kong
BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. METHODS: The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined...
January 25, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29306022/t-regulatory-cells-mediate-immunosuppresion-by-adenosine-in-peripheral-blood-sentinel-lymph-node-and-tils-from-melanoma-patients
#8
P Di Gennaro, G Gerlini, R Caporale, S Sestini, P Brandani, C Urso, N Pimpinelli, L Borgognoni
T regulatory cells (Tregs), involved in tumour tolerance, can generate Adenosine by CD39/CD73 surface enzymes, which identify four Tregs subsets: CD39+CD73- nTregs, CD39+CD73+ iTregs, CD39-CD73+ oTregs and CD39-CD73- xTregs. In melanoma patients, increased Tregs levels are detected in peripheral blood (PB), sentinel lymph node (SLN) and tumour infiltrating lymphocytes (TILs), but Adenosine role was not investigated yet. We examined total Tregs and Adenosine subsets in PB, SLN and TILs from melanoma patients (n = 32) and PB from healthy donors (HD; n = 10) by flow cytometry...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29297928/p21-activated-kinase-2-is-essential-in-maintenance-of-peripheral-foxp3-regulatory-t-cells
#9
Jinyong Choi, David Randall Pease, Siqi Chen, Bin Zhang, Hyewon Phee
The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T cells (tTregs). However, whether Pak2 is required for functions of various subsets of peripheral T cells, such as naïve CD4 and helper T cell subsets including Foxp3+ regulatory T cells (Foxp3+Tregs), is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29282318/src1-promotes-th17-differentiation-by-overriding-foxp3-suppression-to-stimulate-ror%C3%AE-t-activity-in-a-pkc-%C3%AE-dependent-manner
#10
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29282311/a-cellular-microrna-facilitates-regulatory-t-lymphocyte-development-by-targeting-the-foxp3-promoter-tata-box-motif
#11
Yiwen Zhang, Weiwei Liu, Yingshi Chen, Jun Liu, Kang Wu, Lishi Su, Wanying Zhang, Yawen Jiang, Xu Zhang, Yijun Zhang, Chao Liu, Liang Tao, Bingfeng Liu, Hui Zhang
The CD4+CD25+FOXP3+ regulatory T cells (Tregs) mediate immunological self-tolerance and suppress various immune responses. FOXP3 is a key transcriptional factor for the generation and development of Tregs. Its expression is regulated by various cytokines including TGF-β, IL-2, and IL-10. It is important to further identify the regulatory factors for Tregs. Given that many microRNAs (miRNAs) could specifically interact with the core promoter region and specifically enhance the transcription of many target genes, we searched for any possible miRNA(s) targeting the core promoter region of the FOXP3 gene...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29278387/indoleamine-2-3-dioxygenase-ido-enzyme-links-innate-immunity-and-altered-t-cell-differentiation-in-non-st-segment-elevation-acute-coronary-syndrome
#12
Chiara Zara, Anna Severino, Davide Flego, Aureliano Ruggio, Daniela Pedicino, Ada Francesca Giglio, Francesco Trotta, Claudia Lucci, Domenico D'Amario, Ramona Vinci, Eugenia Pisano, Giulio La Rosa, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo
Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS)...
December 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29246441/roquin-suppresses-the-pi3k-mtor-signaling-pathway-to-inhibit-t-helper-cell-differentiation-and-conversion-of-treg-to-tfr-cells
#13
Katharina Essig, Desheng Hu, Joao C Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrabĕ de Angelis, Heinrich Leonhardt, Cornelis F Calkhoven, Elfriede Noessner, Thomas Brocker, Jochen Huehn, Anne B Krug, Mihaela Zavolan, Dirk Baumjohann, Vigo Heissmeyer
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch...
December 12, 2017: Immunity
https://www.readbyqxmd.com/read/29225189/luteolin-attenuates-airway-inflammation-by-inducing-the-transition-of-cd4-cd25-to-cd4-cd25-regulatory-t-cells
#14
Seung-Hyung Kim, Evelyn Saba, Bok-Kyu Kim, Won-Kyung Yang, Yang-Chun Park, Han Jae Shin, Chang Kyun Han, Young Cheol Lee, Man Hee Rhee
Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR)...
February 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29208963/enhanced-cd25-foxp3-regulatory-t-cell-development-by-amodiaquine-through-activation-of-nuclear-receptor-4a
#15
Hee Yeon Won, Ji Hyun Shin, Sera Oh, Hana Jeong, Eun Sook Hwang
CD4+ T cells play key roles in the regulation of immune responses against pathogenic infectious antigens via development into effector T helper and induced regulatory T (iTreg) cells. Particularly, CD4+CD25+Foxp3+ iTreg cells are crucial for maintaining immune homeostasis and controlling inflammatory diseases. Anti-inflammatory drugs that enhance iTreg cell generation would be effective at preventing and treating inflammatory and autoimmune diseases. In this study, we examined whether anti-malarial and anti-arthritic amodiaquine (AQ) could affect iTreg cell development...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180394/redirecting-tgf-%C3%AE-signaling-through-the-%C3%AE-catenin-foxo-complex-prevents-kidney-fibrosis
#16
Xi Qiao, Padmashree Rao, Yun Zhang, Lixin Liu, Min Pang, Hailong Wang, Min Hu, Xinrui Tian, Jianlin Zhang, Ye Zhao, Xin Maggie Wang, Chengshi Wang, Hong Yu, Fei Guo, Qi Cao, Yiping Wang, Yuan Min Wang, Geoff Yu Zhang, Vincent W Lee, Stephen I Alexander, Guoping Zheng, David C H Harris
TGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity...
November 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29143918/induction-of-cd4-cd25-foxp3-regulatory-t-cells-by-mesenchymal-stem-cells-is-associated-with-runx-complex-factors
#17
Maryam Khosravi, Ali Bidmeshkipour, Ali Moravej, Suzzan Hojjat-Assari, Sina Naserian, Mohammad Hossein Karimi
Among the particular immunomodulation properties of mesenchymal stem cells (MSCs), one relies on their capacity to regulatory T cell (Treg) induction from effector T cells. Stable expression of Foxp3 has a dominant role in suppressive phenotype and stability of induced regulatory T cells (iTregs). How MSCs induce stable Foxp3 expression in iTregs remains unknown. We previously showed MSCs could enhance demethylation of Treg-specific demethylated region (TSDR) in iTregs in cell-cell contact manner (unpublished data)...
November 16, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29126851/ccr6-signaling-inhibits-suppressor-function-of-induced-treg-during-gut-inflammation
#18
Neeraja Kulkarni, Heikrujam Thoihen Meitei, Sandip Ashok Sonar, Praveen Kumar Sharma, Vikkarasan Rehman Mujeeb, Sharad Srivastava, Ramanamurthy Boppana, Girdhari Lal
CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3(+)CD4(+) T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6(+) Tregs enhanced the expression of RORγt. The peripheral blood mononuclear cells (PBMCs) of ulcerative colitis (UC) patients showed lower percentages of Foxp3(+)CD4(+) T cells, as compared to healthy individuals, with CCR6(+) Tregs showing higher RORγt expression as compared to CCR6(-)Tregs...
November 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29126272/generation-of-allo-antigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#19
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
December 18, 2017: International Immunology
https://www.readbyqxmd.com/read/29066254/ci8-short-a-novel-lps-induced-peptide-from-the-ascidian-ciona-intestinalis-modulates-responses-of-the-human-immune-system
#20
Angela Bonura, Aiti Vizzini, Sara Vlah, Francesco Gervasi, Alessandra Longo, Mario R Melis, Frank A Schildberg, Paolo Colombo
The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses...
October 16, 2017: Immunobiology
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