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https://www.readbyqxmd.com/read/29900065/the-immune-checkpoint-protein-pd-l1-induces-and-maintains-regulatory-t-cells-in-glioblastoma
#1
Joseph DiDomenico, Jonathan B Lamano, Daniel Oyon, Yuping Li, Dorina Veliceasa, Gurvinder Kaur, Leonel Ampie, Winward Choy, Jason B Lamano, Orin Bloch
Glioblastoma (GBM) promotes immunosuppression through upregulation of PD-L1 and regulatory T cell (Treg) expansion, but the association of these suppressive factors has not been well elucidated. Here, we investigate a role of PD-L1 in expanding Tregs and the value of targeting the PD-1 receptor to inhibit Treg expansion. Quantitative RNA sequencing data from The Cancer Genome Atlas were evaluated for an association between CD274 and FOXP3 transcript expressions and impact of FOXP3 on clinical outcomes. Peripheral leukocytes from patients with newly diagnosed GBM were profiled for PD-L1+ myeloid expressions and Treg abundance...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899562/immunome-differences-between-porcine-ileal-and-jejunal-peyer-s-patches-revealed-by-global-transcriptome-sequencing-of-gut-associated-lymphoid-tissues
#2
T Maroilley, M Berri, G Lemonnier, D Esquerré, C Chevaleyre, S Mélo, F Meurens, J L Coville, J J Leplat, A Rau, B Bed'hom, S Vincent-Naulleau, M J Mercat, Y Billon, P Lepage, C Rogel-Gaillard, J Estellé
The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29867972/transcriptional-control-of-th9-cells-role-of-foxo1-in-interleukin-9-induction
#3
REVIEW
Sakshi Malik, Amit Awasthi
Interleukin (IL) 9-producing helper T (Th) 9 cells play a major role in contributing immunity against extracellular pathogens. In addition, the role of Th9 cells was demonstrated in the pathogenesis of allergic, skin, and intestinal inflammation. The functions of Th9 cells were further extended in antitumor immune response, as Th9 cells were suggested to be potent antitumor Th cells. Given the pleotropic functions of IL-9 in various pathophysiological conditions, it is essential to understand the differentiation and stability of Th9 cells and other IL-9-producing T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29851958/quantitative-proteomic-characterization-and-comparison-of-t-helper-17-and-induced-regulatory-t-cells
#4
Imran Mohammad, Kari Nousiainen, Santosh D Bhosale, Inna Starskaia, Robert Moulder, Anne Rokka, Fang Cheng, Ponnuswamy Mohanasundaram, John E Eriksson, David R Goodlett, Harri Lähdesmäki, Zhi Chen
The transcriptional network and protein regulators that govern T helper 17 (Th17) cell differentiation have been studied extensively using advanced genomic approaches. For a better understanding of these biological processes, we have moved a step forward, from gene- to protein-level characterization of Th17 cells. Mass spectrometry-based label-free quantitative (LFQ) proteomics analysis were made of in vitro differentiated murine Th17 and induced regulatory T (iTreg) cells. More than 4,000 proteins, covering almost all subcellular compartments, were detected...
May 2018: PLoS Biology
https://www.readbyqxmd.com/read/29791021/immtac-anti-pd-1-combination-to-enhance-killing-of-cancer-cells-by-reversing-treg-mediated-immunosuppression
#5
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumor cells have emerged as potentially robust mediators of tumor regression in clinical trials. Two modalities, in particular, bi-specific antibodies for T cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
https://www.readbyqxmd.com/read/29757588/association-of-regulatory-t-cells-with-diabetes-type-1-and-its-renal-and-vascular-complications-based-on-the-expression-of-forkhead-box-protein-p3-foxp3-helios-and-neurophilin-1
#6
Tahereh Khamechian, Behnaz Irandoust, Hanieh Mohammadi, Hassan Nikoueinejad, Hossein Akbari
In recent years, it has been recognized that regulatory T cells (Tregs) play a critical role in maintaining immune tolerance. Moreover, the expression of two markers named Helios and neurophilin-1 (NRP-1) has been highlighted in such cells. Helios, an intracellular transcription marker, largely differentiates twomost operative sub group of Tregs, namely naturally occurring (nTreg) and induced (iTreg) Tregs, and NRP-1 is reckoned as a membranous activity marker of Tregs. We aimed to count peripheral mononuclear cells expressing such markers in a group of type 1 diabetes patients to elucidate the possible role of Tregs in the pathogenesis of such disease and its complications...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29751196/the-significance-role-of-regulatory-t-cells-in-the-persistence-of-infections-by-intracellular-bacteria
#7
REVIEW
Parisa Sabbagh, Ahmad Karkhah, Hamid Reza Nouri, Mostafa Javanian, Soheil Ebrahimpour
Regulatory T cells (Treg cells), are considered as effective immune cells playing a key role in immune response during cancers, autoimmune and infectious diseases. Regulatory T lymphocytes are divided into two main subgroups: natural Treg cells that generated during maturation in the thymus and have the suppressive activity that is critical for the establishment and maintenance of homeostasis in the body and induced Treg cells (iTreg) that are originated from naive T cells following the self-antigen recognition...
May 8, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29743573/foxp3-expression-in-induced-t-regulatory-cells-derived-from-human-umbilical-cord-blood-vs-adult-peripheral-blood
#8
Jeong-Su Do, Fei Zhong, Alex Y Huang, Wouter J Van't Hof, Marcie Finney, Mary J Laughlin
Foxp3 is essential for T regulatory cell (Treg) function. Broad complex-Tramtrack-Bric-a-brac domain (BTB) and Cap'n'collar (CNC) homology 1, transcription factor 2 (BACH2) stabilizes Treg immune homeostasis in murine studies. However, little is known regarding what role, if any, BACH2 may have in Foxp3 regulation in human-induced Treg (iTreg). We examined Foxp3 expression and regulation comparing iTreg differentiated from umbilical cord blood (UCB) vs. adult blood (AB) naive CD4+ T-cells. Foxp3 expression was higher in UCB vs...
May 9, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29730990/time-resolved-transcriptome-and-proteome-landscape-of-human-regulatory-t-cell-treg-differentiation-reveals-novel-regulators-of-foxp3
#9
Angelika Schmidt, Francesco Marabita, Narsis A Kiani, Catharina C Gross, Henrik J Johansson, Szabolcs Éliás, Sini Rautio, Matilda Eriksson, Sunjay Jude Fernandes, Gilad Silberberg, Ubaid Ullah, Urvashi Bhatia, Harri Lähdesmäki, Janne Lehtiö, David Gomez-Cabrero, Heinz Wiendl, Riitta Lahesmaa, Jesper Tegnér
BACKGROUND: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. RESULTS: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation...
May 7, 2018: BMC Biology
https://www.readbyqxmd.com/read/29680746/monocyte-activation-and-inflammation-can-exacerbate-treg-th17-imbalance-in-infants-with-neonatal-necrotizing-enterocolitis
#10
Yin Pang, Xiaoya Du, Xueli Xu, Mengjie Wang, Zhichang Li
Necrotizing enterocolitis (NEC) is a potentially fatal disease that develops in the intestinal tract of newborn infants. An overactive immune system in the intestinal tract of NEC patients not only propagates inflammation and mediates tissue damage, but may also radiate the disease systemically and impose injury to distant organs. We previously identified impairment in the Treg compartment in NEC patients. Here, we hypothesized that monocytes, which could promote iTreg differentiation both in vitro and in vivo, were dysregulated in NEC infants...
June 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29542041/atx-ms-1467-induces-long-term-tolerance-to-myelin-basic-protein-in-dr2-%C3%A3-ob1-f1-mice-by-induction-of-il-10-secreting-itregs
#11
Adriano Luís Soares De Souza, Stefan Rudin, Rui Chang, Keith Mitchell, Timothy Crandall, Shuning Huang, Ji-Kyung Choi, Shinji L Okitsu, Danielle L Graham, Blake Tomkinson, Tammy Dellovade
INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion...
March 14, 2018: Neurology and Therapy
https://www.readbyqxmd.com/read/29535720/t-cell-specific-loss-of-the-pi-3-kinase-p110%C3%AE-catalytic-subunit-results-in-enhanced-cytokine-production-and-antitumor-response
#12
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29484182/regulatory-t-cells-in-renal-disease
#13
REVIEW
Maliha A Alikhan, Megan Huynh, A Richard Kitching, Joshua D Ooi
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen-specific Tregs in HLA-mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype...
2018: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29479348/vitamin-c-fosters-the-in-vivo-differentiation-of-peripheral-cd4-foxp3-t-cells-into-cd4-foxp3-regulatory-t-cells-but-impairs-their-ability-to-prolong-skin-allograft-survival
#14
Karina Oyarce, Mauricio Campos-Mora, Tania Gajardo-Carrasco, Karina Pino-Lagos
Regulatory T cells (Tregs) are critical players of immunological tolerance due to their ability to suppress effector T cell function thereby preventing transplant rejection and autoimmune diseases. During allograft transplantation, increases of both Treg expansion and generation, as well as their stable function, are needed to ensure allograft acceptance; thus, efforts have been made to discover new molecules that enhance Treg-mediated tolerance and to uncover their mechanisms. Recently, vitamin C (VitC), known to regulate T cell maturation and dendritic cell-mediated T cell polarization, has gained attention as a relevant epigenetic remodeler able to enhance and stabilize the expression of the Treg master regulator gene Foxp3, positively affecting the generation of induced Tregs (iTregs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29476742/celastrol-mediates-th17-and-treg-cell-generation-via-metabolic-signaling
#15
Jiabi Zhang, Juan Shan, Xuelu Chen, Shengfu Li, Dan Long, Youping Li
A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+ CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol...
March 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29466736/transcriptional-repressor-hic1-contributes-to-suppressive-function-of-human-induced-regulatory-t-cells
#16
Ubaid Ullah, Syed Bilal Ahmad Andrabi, Subhash Kumar Tripathi, Obaiah Dirasantha, Kartiek Kanduri, Sini Rautio, Catharina C Gross, Sari Lehtimäki, Kanchan Bala, Johanna Tuomisto, Urvashi Bhatia, Deepankar Chakroborty, Laura L Elo, Harri Lähdesmäki, Heinz Wiendl, Omid Rasool, Riitta Lahesmaa
Regulatory T (Treg) cells are critical in regulating the immune response. In vitro induced Treg (iTreg) cells have significant potential in clinical medicine. However, applying iTreg cells as therapeutics is complicated by the poor stability of human iTreg cells and their variable suppressive activity. Therefore, it is important to understand the molecular mechanisms of human iTreg cell specification. We identified hypermethylated in cancer 1 (HIC1) as a transcription factor upregulated early during the differentiation of human iTreg cells...
February 20, 2018: Cell Reports
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
#17
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
#18
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 (TH 17) cells and whose function is dependent on the transcription factor c-MAF...
February 15, 2018: Nature
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#19
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
#20
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...
March 2018: Biotechnology Letters
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