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https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#1
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28993609/transcription-factor-foxo1-is-essential-for-il-9-induction-in-t-helper-cells
#2
Sakshi Malik, Srikanth Sadhu, Srikanth Elesela, Ramendra Pati Pandey, Amanpreet Singh Chawla, Deepak Sharma, Lipsa Panda, Deepak Rathore, Balram Ghosh, Vineet Ahuja, Amit Awasthi
Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3(+) regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1...
October 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28951701/the-role-of-regulatory-t-cells-and-genes-involved-in-their-differentiation-in-pathogenesis-of-selected-inflammatory-and-neoplastic-skin-diseases-part-i-treg-properties-and-functions
#3
REVIEW
Bogusław Nedoszytko, Magdalena Lange, Małgorzata Sokołowska-Wojdyło, Joanna Renke, Piotr Trzonkowski, Michał Sobjanek, Aneta Szczerkowska-Dobosz, Marek Niedoszytko, Aleksandra Górska, Jan Romantowski, Jarosław Skokowski, Leszek Kalinowski, Roman Nowicki
Regulatory T cells (Treg) can be divided into two types: the natural cells (tTreg), which arise in the thymus, and the induced cells (iTreg), which are produced in peripheral tissues during immune response. The most recently published studies indicate that the supervisory functions of these cells are weakened in the pathogenesis of autoimmune and neoplastic diseases of the skin. This may be a result of the domination of other immune cells in the skin, such as Th1/Th17/Th22 and Tc1 type in psoriasis and Th2 in atopic dermatitis...
August 2017: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/28881761/transcription-factor-c-rel-is-indispensable-for-generation-of-thymic-but-not-of-peripheral-foxp3-regulatory-t-cells
#4
Maik Luu, Elena Jenike, Niyati Vachharajani, Alexander Visekruna
The transcription factor c-Rel has been shown to be crucial for development of regulatory T cells (Tregs). Recent studies have reported that the expression of transcription factor Helios in Foxp3(+) Tregs correlates with thymic origin of these cells (tTregs). Notably, we found that only the Helios(+)Foxp3(+) Treg cell population was substantially reduced in c-Rel deficient mice. In contrast to a defective tTreg development, we observed an expansion of mucosal Tregs during the induction of acute colitis in rel(-/-) mice...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28783731/metabolic-control-of-th17-and-induced-treg-cell-balance-by-an-epigenetic-mechanism
#5
Tao Xu, Kelly M Stewart, Xiaohu Wang, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Lu Ni, Saiyong Zhu, Nan Cao, Dongwei Zhu, Yu Zhang, Katerina Akassoglou, Chen Dong, Edward M Driggers, Sheng Ding
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells...
August 10, 2017: Nature
https://www.readbyqxmd.com/read/28759565/low-doses-of-cholera-toxin-and-its-mediator-camp-induce-ctla-2-secretion-by-dendritic-cells-to-enhance-regulatory-t-cell-conversion
#6
Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen, Thomas Reinheckel, Thomas D Mueller, Jochen Bodem, Manfred B Lutz
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β)...
2017: PloS One
https://www.readbyqxmd.com/read/28736999/regulatory-t-cell-subsets-in-peripheral-blood-of-celiac-disease-patients-and-tlr2-expression-correlation-with-oxidative-stress
#7
Sanjay Kumar, Sadhna Lal, Archana Bhatnagar
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls...
October 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#8
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28732437/effect-of-microrna-21-transfection-on-in-vitro-differentiation-of-human-naive-cd4-t-cells-to-regulatory-t-cells
#9
Haideh Namdari, Mojgan Ghayedi, Jamshid Hadjati, Farhad Rezaei, Kurosh Kalantar, Parisa Rahimzadeh, Eisa Salehi
Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28729608/programmed-death-one-homolog-maintains-the-pool-size-of-regulatory-t-cells-by-promoting-their-differentiation-and-stability
#10
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710254/the-plasticity-and-stability-of-regulatory-t-cells-during-viral-induced-inflammatory-lesions
#11
Siddheshvar Bhela, Siva Karthik Varanasi, Ujjaldeep Jaggi, Sarah S Sloan, Naveen K Rajasagi, Barry T Rouse
Ocular infection with HSV causes a chronic T cell-mediated inflammatory lesion in the cornea. Lesion severity is affected by the balance of different CD4 T cell subsets, with greater severity occurring when the activity of regulatory T cells (Tregs) is compromised. In this study, fate-mapping mice were used to assess the stability of Treg function in ocular lesions. We show that cells that were once Foxp3(+) functional Tregs may lose Foxp3 and become Th1 cells that could contribute to lesion expression. The instability primarily occurred with IL-2R(lo) Tregs and was shown, in part, to be the consequence of exposure to IL-12...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28702462/adoptive-cell-therapy-of-induced-regulatory-t-cells-expanded-by-tolerogenic-dendritic-cells-on-murine-autoimmune-arthritis
#12
Jie Yang, Lidong Liu, Yiming Yang, Ning Kong, Xueyu Jiang, Juan Sun, Rufeng Xie
OBJECTIVE: Tolerogenic dendritic cells (tDCs) can expand TGF-β-induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. METHODS: After induction by TGF-β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed by flow cytometry...
2017: Journal of Immunology Research
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
#13
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/28677759/analysis-of-murine-and-human-treg-subsets-in-inflammatory-bowel-disease
#14
Xiaoyun Sun, Shaoheng He, Changlong Lv, Xun Sun, Junling Wang, Wenjiao Zheng, Danan Wang
Previous studies have indicated that regulatory T cells serve essential roles in maintaining intestinal homeostasis, however, the role of different Treg subsets in modulating inflammatory bowel disease has still not been addressed clearly. In the present study, the authors measured the percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs, Foxp3‑ IL‑10+ TGF‑β‑ induced Tregs, CD127‑ induced Tregs and CD8+ Tregs at different time points in DSS‑induced experimental colitis model in murine lamina propria lymphocytes, mesenteric lymph node and peripheral blood...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28652577/human-in-vitro-induced-regulatory-t-cells-display-dlgh1dependent-and-pkc-%C3%AE-restrained-suppressive-activity
#15
Alexandra Zanin-Zhorov, Sudha Kumari, Keli L Hippen, Sarah C Merkel, Margaret L MacMillan, Bruce R Blazar, Michael L Dustin
In vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620241/tgf-beta-atra-induced-tregs-express-a-selected-set-of-micrornas-involved-in-the-repression-of-transcripts-related-to-th17-differentiation
#16
Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Felipe Saldanha-Araujo, João Baiochi, Amélia Goes Araujo, Priscila Santos Scheucher, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA)...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600182/mesenchymal-stem-cells-can-induce-regulatory-t-cells-via-modulating-mir-126a-but-not-mir-10a
#17
Maryam Khosravi, Mohammad Hossein Karimi, Mahdokht Hossein Aghdaie, Mehdi Kalani, Sina Naserian, Ali Bidmeshkipour
Among the different immunosuppressive properties attributed to mesenchymal stem cells (MSCs), one relies on their ability to induce regulatory T cells (iTregs) from conventional T cells under particular inflammatory context. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, the mechanism behind Foxp3 induction in iTregs by MSCs remains unknown. Here, we assessed the possible effect of MSCs on miR-126a and miR-10a expression in iTregs and, consequently on Foxp3 stability, a regulatory pathway that has not yet been explored...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#18
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28598443/ash1l-and-lnc-smad3-coordinate-smad3-locus-accessibility-to-modulate-itreg-polarization-and-t-cell-autoimmunity
#19
Meng Xia, Juan Liu, Shuxun Liu, Kun Chen, Hongyu Lin, Minghong Jiang, Xiaoqing Xu, Yiquan Xue, Wei Liu, Yan Gu, Xiang Zhang, Zhiqing Li, Lin Yi, Youcun Qian, Chen Zhou, Ru Li, Xuan Zhang, Zhanguo Li, Xuetao Cao
Regulatory T (Treg) cells are important for the maintenance of immune homoeostasis and prevention of autoimmune diseases. Epigenetic modifications have been reported to modulate autoimmunity by altering Treg cell fate. Here we show that the H3K4 methyltransferase Ash1l facilitates TGF-β-induced Treg cell polarization in vitro and protects mice from T cell-mediated colitis in vivo. Ash1l upregulates Smad3 expression by directly targeting Smad3 promoter to increase local H3K4 trimethylation. Furthermore, we identify an lncRNA, namely lnc-Smad3, which interacts with the histone deacetylase HDAC1 and silences Smad3 transcription...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28579377/dendritic-cells-conditioned-by-activin-a-induced-regulatory-t-cells-exhibit-enhanced-tolerogenic-properties-and-protect-against-experimental-asthma
#20
Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Dimitris Konstantopoulos, Marina Adamou-Tzani, Tim Sparwasser, Georgina Xanthou
BACKGROUND: Previously, we have demonstrated that regulatory T (Treg) cells, induced by the cytokine activin-A, suppress Th2-mediated allergic responses and linked airway disease. Still, the effects of activin-A-induced Treg cells (act-A-iTreg cells) on the regulation of dendritic cell (DC)-driven allergic inflammation remain elusive. OBJECTIVE: Here, we investigated whether act-A-iTreg cells can modulate DC responses and endow them with enhanced tolerogenic functions...
June 1, 2017: Journal of Allergy and Clinical Immunology
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