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https://www.readbyqxmd.com/read/29458119/the-function-of-hla-b-13-01-involved-in-the-pathomechanism-of-dapsone-induced-severe-cutaneous-adverse-reactions
#1
Wei-Ti Chen, Chuang-Wei Wang, Chun-Wei Lu, Chun-Bing Chen, Hua-En Lee, Shuen-Iu Hung, Siew-Eng Choon, Chih-Hsun Yang, Ming-Tsan Liu, Ting Jui Chen, Wen-Lang Fan, Shih-Chi Su, Yang Yu-Wei Lin, Ya-Ching Chang, Wen-Hung Chung
Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions (SCAR), such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remains unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells (CTLs) involved in pathogenesis of dapsone-SCAR...
February 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29458078/isolation-of-intact-rna-from-murine-cd4-t-cells-after-intracellular-cytokine-staining-and-fluorescence-activated-cell-sorting
#2
Shajo Kunnath-Velayudhan, Steven A Porcelli
Intracellular cytokine staining (ICS) is a powerful method for identifying functionally distinct lymphocyte subsets, and for isolating these by fluorescence activated cell sorting (FACS). Although transcriptomic analysis of cells sorted on the basis of ICS has many potential applications, this is rarely performed because of the difficulty in isolating intact RNA from cells processed using standard fixation and permeabilization buffers for ICS. To address this issue, we compared three buffers shown previously to preserve RNA in nonhematopoietic cells subjected to intracellular staining for their effects on RNA isolated from T lymphocytes processed for ICS...
February 17, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29458010/galectin-9-is-critical-for-mucosal-adaptive-immunity-through-the-t-h-17-iga-axis
#3
Chih-Chia Liang, Chi-Shan Li, I-Chun Weng, Huan-Yuan Chen, Hsueh-Han Lu, Chiu-Ching Huang, Fu-Tong Liu
Impairment of the intestinal mucosal immunity significantly increases the risk of acute and chronic diseases. Immunoglobulin A (IgA) plays a major role in humoral mucosal immunity to provide protection against pathogens and toxins in the gut. Here, we investigated the role of endogenous galectin-9, a tandem repeat-type β-galactoside-binding protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/- and littermate control mice, it was found that lack of galectin-9 impaired mucosal antigen-specific IgA response in the gut...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457898/synthesis-and-biological-evaluation-of-e-4-hydroxy-3-methylbut-2-enyl-phosphate-hmbp-aryloxy-triester-phosphoramidate-prodrugs-as-activators-of-v%C3%AE-9-v%C3%AE-2-t-cells-immune-response
#4
Martin S Davey, Roshni Malde, Rory C Mykura, Alfie T Baker, Taher E Taher, Cécile S Le Duff, Benjamin E Willcox, Youcef Mehellou
The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics.
February 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29457550/mir-505-3p-controls-chemokine-receptor-up-regulation-in-macrophages-role-in-familial-hypercholesterolemia
#5
Rafael Escate, Pedro Mata, Jose Maria Cepeda, Teresa Padró, Lina Badimon
Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs)...
February 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29457375/evidence-for-alternate-modes-of-b-cell-activation-involving-fab-acquired-n-glycosylations-in-antibody-secreting-cells-infiltrating-the-labial-salivary-glands-of-sj%C3%A3-gren-s-syndrome-patients
#6
Kristi A Koelsch, Joshua Cavett, Kenneth Smith, Jacen S Moore, Sylvain D Lehoux, Nan Jia, Tim Mather, Syed M S Quadri, Astrid Rasmussen, C Erick Kaufman, David M Lewis, Lida Radfar, Teresa A Scordino, Christopher J Lessard, Biji T Kurien, Richard D Cummings, Judith A James, Kathy L Sivils, A Darise Farris, R Hal Scofield
OBJECTIVE: To better understand the role of B cells, potential mechanisms for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's Syndrome (SS), we explored selection pressures and N-glycosylation acquired by somatic mutation (acN-glyc) in the immunoglobulin (Ig) variable regions (V-regions) of antibody secreting cells (ASCs) isolated from the minor salivary glands of SS patients and non-SS controls with sicca symptoms. METHODS: We report a novel method to produce and characterize recombinant monoclonal antibodies (mAbs) from SS patient and control labial salivary gland single-cell sorted ASC infiltrates that can be utilized to concurrently probe any other expressed genes...
February 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29456657/intramuscular-primary-immunization-by-nucleic-acid-vaccine-pcdna-gpd-il-2-and-enhanced-immunization-with-mucosal-adjuvant-cpg-odn-and-gpd-il-2-recombinant-protein-effectively-induced-strong-mucosal-immune-responses-and-immune-protective-effects-against-treponema
#7
Xiaohong Zhang, Tie Zhao, Tiebing Zeng, Ning Wu, Yongjian Xiao, Shuangquan Liu, Jian Yu, Chuanhao Jiang, Lin Gan, Meixia Deng, Xi Luo, Feijun Zhao
The present study aimed to evaluate the immune effect of intramuscular primary immunization by the nucleic acid vaccine pcDNA/glycerophosphodiester phosphodiesterase-interleukin-2 (pcDNA/Gpd-IL-2) and enhanced immunization 2 weeks later with the combination of mucosal adjuvant CpG-oligodeoxynucleotides (ODN) and Gpd-IL-2 recombinant protein on skin infection caused by Treponema pallidum (Tp) in New Zealand rabbits. At week 8 following immunization, MTT assay was used to detect spleen cell proliferation, while enzyme-linked immunosorbent assay was performed to detect the cytokine and secretory immunoglobulin A (SIgA) levels...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456655/effect-of-immune-tolerance-induced-by-immature-dendritic-cells-and-ctla4-ig-on-systemic-lupus-erythematosus-an-in-vivo-study
#8
Cuili Huang, Lidan Zhang, Fang Ling, Sijian Wen, Yanyan Luo, Hui Liu, Jingping Liu, Wenjun Zheng, Ming Liang, Jian Sun, You-Kun Lin
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456652/analysis-of-the-levels-of-th9-cells-and-cytokines-in-the-peripheral-blood-of-mice-with-bronchial-asthma
#9
Ruifang Tong, Liping Xu, Lihong Liang, Han Huang, Rui Wang, Yinghui Zhang
The purpose of the study was to detect the level of T-helper type 9 (Th9) cells and the cytokine interleukin-9 (IL-9) in peripheral blood of mice with bronchial asthma, and to explore the relationship between the expression of Th9 cells and the pathogenesis of asthma. Thirty female-specific pathogen-free (SPF) Bagg' albino (BALB)/c mice were selected and randomly divided into the control group (n=15) and the bronchial observation group (n=15). Mice in the bronchial observation group were treated with ovalbumin (OVA) for sensitization and induction of a mouse model of asthma...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#10
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456530/donor-genotype-in-the-interleukin-7-receptor-%C3%AE-chain-predicts-risk-of-graft-versus-host-disease-and-cytomegalovirus-infection-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
Katrine Kielsen, Christian Enevold, Carsten Heilmann, Henrik Sengeløv, Anders Elm Pedersen, Lars P Ryder, Klaus Müller
The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus and peripheral T cell homeostasis. In this study, we investigated the impact of the single nucleotide polymorphism rs6897932 in the IL-7 receptor α-chain (IL-7Rα) which has previously been associated with several autoimmune diseases...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456508/the-molecular-determinants-of-small-molecule-ligand-binding-at-p2x-receptors
#12
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29456181/an-ultraconserved-element-containing-lncrna-preserves-transcriptional-dynamics-and-maintains-esc-self-renewal
#13
Alessandro Fiorenzano, Emilia Pascale, Miriam Gagliardi, Sara Terreri, Mariarosaria Papa, Gennaro Andolfi, Marco Galasso, Guidantonio Malagoli Tagliazucchi, Cristian Taccioli, Eduardo Jorge Patriarca, Amelia Cimmino, Maria Rosaria Matarazzo, Gabriella Minchiotti, Annalisa Fico
Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics...
February 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456159/cd150-high-bone-marrow-tregs-maintain-hematopoietic-stem-cell-quiescence-and-immune-privilege-via-adenosine
#14
Yuichi Hirata, Kazuhiro Furuhashi, Hiroshi Ishii, Hao Wei Li, Sandra Pinho, Lei Ding, Simon C Robson, Paul S Frenette, Joji Fujisaki
A crucial player in immune regulation, FoxP3+ regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence...
February 7, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29456158/autologous-ipsc-based-vaccines-elicit-anti-tumor-responses-in-vivo
#15
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29456015/multi-antigenic-human-cytomegalovirus-mrna-vaccines-that-elicit-potent-humoral-and-cell-mediated-immunity
#16
Shinu John, Olga Yuzhakov, Angela Woods, Jessica Deterling, Kimberly Hassett, Christine A Shaw, Giuseppe Ciaramella
A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers...
February 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29455951/sex-hormone-contributes-to-sexually-dimorphic-susceptibility-in-cvb3-induced-viral-myocarditis-via-modulating-ifn-%C3%AE-nk-cell-production
#17
Nannan Zhou, Yan Yue, Sidong Xiong
BACKGROUND: Viral myocarditis is a widespread cardiac disease associated with inflammation and myocardial injury and is predominantly caused by coxsackievirus B3 (CVB3) infection in humans as well as in mice. CVB3-induced myocarditis shows sexually dimorphic sensitivity and is more prevalent in male mice. Our previous studies showed that natural killer (NK) cells played an indispensable role in CVB3-induced myocarditis, and female mice exhibited less pathological cardiac interferon gamma (IFN-γ)+ NK cell infiltration than did male mice...
January 6, 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29455908/increased-degradation-of-atp-is-driven-by-memory-regulatory-t-cells-in-kidney-transplantation-tolerance
#18
Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process...
February 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29455848/caveolin-1-the-unnoticed-player-in-tcr-and-bcr-signaling
#19
Gina J Fiala, Susana Minguet
T and B lymphocytes are key players of the adaptive immune system. They recognize pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR) to get activated and execute their protective function. TCR and BCR signaling are initiated at the plasma membrane and subsequently propagated into the cell, ultimately leading to cell activation and a protective immune response. However, inappropriate activation of T and B cells can be detrimental to the host resulting in autoimmune disorders, immunodeficiencies, and cancer...
2018: Advances in Immunology
https://www.readbyqxmd.com/read/29455845/single-cell-resolution-of-t-cell-immune-responses
#20
Veit R Buchholz, Michael Flossdorf
Single antigen-specific B or T lymphocytes are the smallest functional units, into which an adaptive immune response can be dissected. Today, novel high-throughput technologies are providing researches with increasingly complex information on the diverse phenotypic signatures of individual lymphocytes. With a focus on T cells, we summarize here, how computational approaches are becoming increasingly important to identify the relevant developmental boundaries and connections between these high-dimensional lymphocyte states...
2018: Advances in Immunology
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