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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
#1
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
#2
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
#3
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
#4
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
#5
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...
February 21, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
February 13, 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
#13
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
#14
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...
March 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29297928/p21-activated-kinase-2-is-essential-in-maintenance-of-peripheral-foxp3-regulatory-t-cells
#15
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 (Treg) cells. However, whether Pak2 is required for the functions of various subsets of peripheral T cells, such as naive CD4 and helper T-cell subsets including Foxp3+ Treg cells, 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
#16
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...
January 16, 2018: 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
#17
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...
February 1, 2018: 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
#18
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
#19
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 19, 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
#20
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
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