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https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#1
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
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/27888331/the-origin-of-dcs-and-capacity-for-immunologic-tolerance-in-central-and-peripheral-tissues
#3
REVIEW
K Sanjana P Devi, Niroshana Anandasabapathy
Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu, multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells...
November 25, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27882863/porphyromonas-gingivalis-suppresses-adaptive-immunity-in-periodontitis-atherosclerosis-and-alzheimer-s-disease
#4
REVIEW
Ingar Olsen, Martin A Taubman, Sim K Singhrao
Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host's adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions...
2016: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/27878210/t-regulatory-cell-mediated-immunotherapy-for-solid-organ-transplantation-a-clinical-perspective
#5
Mohammad Afzal Khan
T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection...
November 22, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27876361/beneficial-effects-of-galectin-9-on-allergen-specific-sublingual-immunotherapy-in-a-dermatophagoides-farinae-induced-mouse-model%C3%A2-of-chronic-asthma
#6
Masaki Ikeda, Shigeki Katoh, Hiroki Shimizu, Akira Hasegawa, Katsuyo Ohashi-Doi, Mikio Oka
BACKGROUND: Allergen-specific sublingual immunotherapy is a potential disease-modifying treatment for allergic asthma. Galectin-9 (Gal-9), a β-galactoside-binding protein with various biologic effects, acts as an immunomodulator in excessive immunologic reactions by expanding regulatory T cells (Treg) and enhancing transforming growth factor (TGF)-β signaling. We investigated the efficacy of sublingually administered Gal-9 as an adjuvant to a specific allergen in a Dermatophagoides farinae (Df)-induced mouse model of chronic asthma...
November 19, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/27876058/a-novel-non-hodgkin-lymphoma-murine-model-closer-to-the-standard-clinical-scenario
#7
Thais Bascuas, María Moreno, Amy Mónaco, Laura Reyes, Andrea Paolino, Patricia Oliver, María G Kramer, Henry Engler, José P Pacheco, Sofía Grille, José A Chabalgoity
BACKGROUND: Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological malignancies. Despite recent major advances in treatment, a substantial proportion of patients relapses highlighting the need for new therapeutic modalities. Promissory results obtained in pre-clinical studies are usually not translated when moving into clinical trials. Pre-clinical studies are mainly conducted in animals with high tumor burden; instead patients undergo chemotherapy as first line of treatment and most likely are under remission when immunotherapies are applied...
November 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27865421/cannabidiol-cbd-induces-functional-tregs-in-response-to-low-level-t-cell-activation
#8
Saphala Dhital, John V Stokes, Nogi Park, Keun Seok Seo, Barbara L F Kaplan
Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been described in immune responses induced by strong immunological stimuli. It has also been shown that CBD enhances IL-2 production in response to low-level T cell stimulation. Since IL-2, in combination with TGF-β1, are critical for Treg induction, we hypothesized that CBD would induce CD4(+)CD25(+)FOXP3(+) Tregs in response to low-level stimulation. Low-level T cell stimulation conditions were established based on minimal CD25 expression in CD4(+) cells using suboptimal PMA/Io (4nM/0...
November 9, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27865385/the-characteristic-profiles-of-pd-1-and-pd-l1-expressions-and-dynamic-changes-during-treatment-in-active-tuberculosis
#9
Lei Shen, Hong Shi, Yan Gao, Qinfang Ou, Qianqian Liu, Yuanyuan Liu, Jing Wu, Wenhong Zhang, Lin Fan, Lingyun Shao
PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD)...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#10
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#11
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27833451/heat-shock-proteins-hsps-in-the-homeostasis-of-regulatory-t-cells-tregs
#12
REVIEW
Tomasz Koliński, Natalia Marek-Trzonkowska, Piotr Trzonkowski, Janusz Siebert
Heat shock proteins (HSPs) belong to the family of conservative polypeptides with a high homology of the primary structure. The uniqueness of this family lies in their ability to interact with a large number of different proteins and provide protection from cellular and environmental stress factors as molecular chaperones to keep protein homeostasis. While intracellular HSPs play a mainly protective role, extracellular or membrane-bound HSPs mediate immunological functions and immunomodulatory activity. In immune system are subsets of cells including regulatory T cells (Tregs) with suppressive functions...
2016: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/27826960/oral-food-desensitization-in-children-with-ige-mediated-cow-s-milk-allergy-immunological-changes-underlying-desensitization
#13
Laura Perezábad, Marta Reche, Teresa Valbuena, Rosina López-Fandiño, Elena Molina, Iván López-Expósito
PURPOSE: This study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population. METHODS: A group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited...
January 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/27817178/roles-of-regulatory-t-and-b-cells-in-igg4-related-disease
#14
Kazushige Uchida, Kazuichi Okazaki
Immunoglobulin G4 (IgG4) -related disease (RD) is a newly recognized systemic disease. Although there are several forms of IgG4-RD reported under various names, depending on the target organ and characteristics, patients with IgG4-RD manifest several immunologic and histologic abnormalities including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. However, the pathophysiology remains unclear. Regulatory immune cells play an important role in several immune-related diseases...
November 6, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/27798870/immunological-and-clinical-impact-of-cancer-stem-cells-in-vulvar-cancer-role-of-cd133-cd24-abcg2-expressing-cells
#15
Chiara Napoletano, Filippo Bellati, Ilary Ruscito, Milena Pernice, Ilaria Grazia Zizzari, Salvatore Caponnetto, Federica Tomao, Luigi Frigerio, Marco Liberati, Aurelia Rughetti, Donatella Caserta, Pierluigi Benedetti Panici, Marianna Nuti
BACKGROUND: Cancer stem cells (CSCs) are tumour-initiating cells with self-renewal properties and chemo/radio-resistance. Regulatory T-cells (Tregs) influence CSCs through several mechanisms. In different solid tumours, the presence of both cell populations correlated with poor survival. In vulvar cancer, little is known regarding biological markers able to predict patient prognosis. We investigated the presence and clinical impact of CSCs and infiltrating Treg in primary vulvar cancer...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27788149/transcriptional-profiling-of-egg-allergy-and-relationship-to-disease-phenotype
#16
Roman Kosoy, Charuta Agashe, Alexander Grishin, Donald Y Leung, Robert A Wood, Scott H Sicherer, Stacie M Jones, A Wesley Burks, Wendy F Davidson, Robert W Lindblad, Peter Dawson, Miriam Merad, Brian A Kidd, Joel T Dudley, Hugh A Sampson, M Cecilia Berin
BACKGROUND: Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE. OBJECTIVE: To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic...
2016: PloS One
https://www.readbyqxmd.com/read/27782139/antibiotic-mediated-gut-microbiome-perturbation-accelerates-development-of-type-1-diabetes-in-mice
#17
Alexandra E Livanos, Thomas U Greiner, Pajau Vangay, Wimal Pathmasiri, Delisha Stewart, Susan McRitchie, Huilin Li, Jennifer Chung, Jiho Sohn, Sara Kim, Zhan Gao, Cecily Barber, Joanne Kim, Sandy Ng, Arlin B Rogers, Susan Sumner, Xue-Song Zhang, Ken Cadwell, Dan Knights, Alexander Alekseyenko, Fredrik Bäckhed, Martin J Blaser
The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures...
August 22, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27765952/immunology-metabolic-changes-modify-treg-cell-function
#18
Sarah Onuora
No abstract text is available yet for this article.
October 21, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27759466/treg-cells-in-cancer-beyond-classical-immunological-control
#19
Paula D Bos
A prerequisite for tumor evolution toward a malignant state is the establishment of cell intrinsic and extrinsic mechanisms of immune suppression (Hanahan and Weinberg, 2000, 2011; Schreiber, Old, and Smyth, 2011). Widespread recruitment of Foxp3(+) regulatory T cells (TREG) is a prevailing means to dampen antitumor immunity. Advances in the characterization of TREG cell heterogeneity and physiological function of tissue resident TREG cells unfold new possibilities for nontraditional tumor-promoting functions of intratumoral TREG cells...
October 19, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27757302/evaluation-of-immune-infiltration-in-the-colonic-mucosa-of-patients-with-ipilimumab-related-colitis
#20
Edurne Arriola, Matthew Wheater, Maria Antonette Lopez, Gareth Thomas, Christian Ottensmeier
Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8(+), FoxP3, and granzyme B (GzmB) in colonic biopsies from 20 patients with ipilimumab-related colitis. We assessed 10 cases with normal colon biopsies for comparison...
2016: Oncoimmunology
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