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https://www.readbyqxmd.com/read/28210258/human-gingiva-derived-mesenchymal-stem-cells-inhibit-xeno-graft-versus-host-disease-via-cd39-cd73-adenosine-and-ido-signals
#1
Feng Huang, Maogen Chen, Weiqian Chen, Jian Gu, Jia Yuan, Yaoqiu Xue, Junlong Dang, Wenru Su, Julie Wang, Homayoun H Zadeh, Xiaoshun He, Limin Rong, Nancy Olsen, Song Guo Zheng
Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28203772/elevated-pre-art-cd39-cd8-t-cell-frequency-is-associated-with-early-mortality-in-advanced-hiv-tb
#2
Shruthi Ravimohan, Neo Tamuhla, Kebatshabile Nfanyana, Houping Ni, Andrew P Steenhoff, Robert Gross, Drew Weissman, Gregory P Bisson
No abstract text is available yet for this article.
February 16, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28198766/the-differential-effect-of-apyrase-treatment-and-hcd39-overexpression-on-chronic-renal-fibrosis-following-ischemia-reperfusion-injury
#3
Veena Roberts, Duncan J Campbell, Bo Lu, Joanne Chia, Peter J Cowan, Karen M Dwyer
BACKGROUND: Renal ischemia reperfusion injury (IRI) leads to acute kidney injury and renal fibrosis. CD39 is a key purinergic enzyme in the hydrolysis of ATP and increased CD39 enzymatic activity protects from acute IRI but its effect on renal fibrosis is not known. METHODS: Using a mouse model of unilateral renal IRI, the effects of increased CD39 activity (using soluble apyrase and mice expressing human CD39 transgene) on acute and chronic renal outcomes were examined...
February 14, 2017: Transplantation
https://www.readbyqxmd.com/read/28193736/down-regulation-of-cd73-on-b-cells-of-patients-with-viremic-hiv-correlates-with-b-cell-activation-and-disease-progression
#4
Eun-Seong Kim, Christin Ackermann, Ilona Tóth, Patrick Dierks, Johanna M Eberhard, Raluca Wroblewski, Felix Scherg, Matthias Geyer, Reinhold E Schmidt, Claudia Beisel, Maximilian Bockhorn, Friedrich Haag, Jan van Lunzen, Julian Schulze Zur Wiesch
Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0...
February 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28182700/pilot-double-blind-randomized-placebo-controlled-clinical-trial-of-the-supplement-food-nyaditum-resae%C3%A2-in-adults-with-or-without-latent-tb-infection-safety-and-immunogenicity
#5
Eva Montané, Ana Maria Barriocanal, Ana Lucía Arellano, Angelica Valderrama, Yolanda Sanz, Nuria Perez-Alvarez, Paula Cardona, Cristina Vilaplana, Pere-Joan Cardona
BACKGROUND: Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. METHODS: Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30)...
2017: PloS One
https://www.readbyqxmd.com/read/28174424/targeting-a2-adenosine-receptors-in-cancer
#6
REVIEW
David Allard, Martin Turcotte, John Stagg
Tumor cells use various ways to evade antitumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine-generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate antitumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro-angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer...
February 8, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28155899/fingolimod-alters-the-transcriptome-profile-of-circulating-cd4-cells-in-multiple-sclerosis
#7
Jörg Friess, Michael Hecker, Luisa Roch, Dirk Koczan, Brit Fitzner, Ines Charlotte Angerer, Ina Schröder, Kristin Flechtner, Hans-Jürgen Thiesen, Alexander Winkelmann, Uwe Klaus Zettl
Multiple sclerosis is a demyelinating disease affecting the central nervous system. T cells are known to contribute to this immune-mediated condition. Fingolimod modulates sphingosine-1-phosphate receptors, thereby preventing the egress of lymphocytes, especially CCR7-expressing CD8+ and CD4+ T cells, from lymphoid tissues. Using Affymetrix Human Transcriptome Arrays (HTA 2.0), we performed a transcriptome profiling analysis of CD4+ cells obtained from the peripheral blood of patients with highly active relapsing-remitting multiple sclerosis...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28154567/phenotypic-alterations-involved-in-cd8-treg-impairment-in-systemic-sclerosis
#8
Simone Negrini, Daniela Fenoglio, Alessia Parodi, Francesca Kalli, Florinda Battaglia, Giorgia Nasi, Monica Curto, Samuele Tardito, Francesca Ferrera, Gilberto Filaci
Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis, vasculopathy, and autoimmunity. Although the exact pathogenetic mechanisms behind SSc remain to be fully elucidated, a great deal of evidence suggests the existence of an unbalanced ratio between the effector and regulatory arms of the immune system. With regard to the T regulatory (Treg) compartment, we observed that CD8+ Treg subsets display functional defects in SSc-affected patients. Since CD127 down-modulation and CD39 upregulation have been observed on Treg subsets, the phenotypic expression of these molecules was analyzed on the CD8+CD28- Treg precursors and on CD8+ Treg cells generated in vitro through interleukin-10 commitment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28111965/identification-of-cd4-t-cell-derived-cd161-cd39-and-cd39-cd73-microparticles-as-new-biomarkers-for-rheumatoid-arthritis
#9
Wenqiang Fan, Wenxiang Wang, Jie Wu, Ling Ma, Jinyan Guo
AIM: This study aimed to identify CD4(+) T-cell-derived microparticles (MPs) and investigate their roles in rheumatoid arthritis (RA). METHODS: Synovial fluids from 34 RA, 33 osteoarthritis patients and 42 healthy individuals were analyzed by flow cytometry. Human fibroblast-like synoviocytes and peripheral blood mononuclear cells were cultured with or without isolated MPs, chemokines and cytokines were measured by ELISA. RESULTS: CD4(+)CD161(+)CD39(+) and CD4(+)CD39(+)CD73(+) MPs were abundantly present in RA patients, which were positively or negatively correlated with RA features, respectively...
February 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28097233/ectonucleotidase-cd39-driven-control-of-postinfarction-myocardial-repair-and-rupture
#10
Nadia R Sutton, Takanori Hayasaki, Matthew C Hyman, Anuli C Anyanwu, Hui Liao, Danica Petrovic-Djergovic, Linda Badri, Amy E Baek, Natalie Walker, Keigo Fukase, Yogendra Kanthi, Scott H Visovatti, Ellen L Horste, Jessica J Ray, Sascha N Goonewardena, David J Pinsky
Mechanical complications of myocardial infarction (MI) are often fatal. Little is known about endogenous factors that predispose to myocardial rupture after MI. Ectonucleoside triphosphate diphosphohydrolase (CD39) could be a critical mediator of propensity to myocardial rupture after MI due to its role in modulating inflammation and thrombosis. Using a model of permanent coronary artery ligation, rupture was virtually abrogated in cd39(-/-) mice versus cd39(+/+) controls, with elevated fibrin and collagen deposition and marked neutrophil and macrophage influx...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28093236/extracellular-atp-and-adenosine-the-yin-and-yang-in-immune-responses
#11
REVIEW
M M Faas, T Sáez, P de Vos
Extracellular adenosine 5'-triphosphate (ATP) and adenosine molecules are intimately involved in immune responses. ATP is mostly a pro-inflammatory molecule and is released during hypoxic condition and by necrotic cells, as well as by activated immune cells and endothelial cells. However, under certain conditions, for instance at low concentrations or at prolonged exposure, ATP may also have anti-inflammatory properties. Extracellular ATP can activate both P2X and P2Y purinergic receptors. Extracellular ATP can be hydrolyzed into adenosine in a two-step enzymatic process involving the ectonucleotidases CD39 (ecto-apyrase) and CD73...
January 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28087077/alteration-of-cd39-foxp3-cd4-t-cell-and-cytokine-levels-in-eae-ms-following-anti-cd52-treatment
#12
Anudeep B Pant, Yan Wang, Daniel W Mielcarz, Eli J Kasper, Kiel M Telesford, Megan Mishra, Azizul Haque, Jacqueline Smith, Lloyd H Kasper, Sakhina Begum-Haque
While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39+ Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4+CD39+ Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb...
December 21, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#13
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28060378/cd73-regulates-anti-inflammatory-signaling-between-apoptotic-cells-and-endotoxin-conditioned-tissue-macrophages
#14
Patrick S Murphy, Jing Wang, Samir P Bhagwat, Joshua C Munger, William J Janssen, Terry W Wright, Michael R Elliott
The phagocytosis of apoptotic cells (efferocytosis) shifts macrophages to an anti-inflammatory state through a set of still poorly understood soluble and cell-bound signals. Apoptosis is a common feature of inflamed tissues, and efferocytosis by tissue macrophages is thought to promote the resolution of inflammation. However, it is not clear how the exposure of tissue macrophages to inflammatory cues (e.g., PAMPs, DAMPs) in the early stages of inflammation affects immune outcomes of macrophage-apoptotic cell interactions occurring at later stages of inflammation...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28060121/the-sickle-%C3%AE-thalassemia-phenotype
#15
Adekunle D Adekile, Nagihan Akbulut, Asmaa F Azab, Sundus Al-Sharida, Diana Thomas
Sβ-thalassemia (Sβ-thal) is common among Gulf Arab patients with sickle cell disease, but the phenotype of this group had not been well-documented. We have studied a group of Kuwaiti patients and compared the phenotype in the homozygotes (SS) and Sβ-thal patients. Complete blood count, hemoglobin quantitation, serum bilirubin, and lactate dehydrogenase were determined with standard techniques. The patients were screened for α-globin genotype. The Sβ-thal patients were also screened for the HBG2 Xmn-1 polymorphism...
January 5, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28043488/development-of-the-food-supplement-nyaditum-resae-as-a-new-tool-to-reduce-the-risk-of-tuberculosis-development
#16
Nestani Tukvadze, Paula Cardona, Sergo Vashakidze, Natalia Shubladze, Zaza Avaliani, Cris Vilaplana, Pere-Joan Cardona
Nyaditum resae (NR) is a galenic preparation of heat-killed Mycobacterium manresensis (hkMn). This is a new species that belongs to the Mycobacterium fortuitum complex, and it is present in drinking water-thus, regulatorily speaking, it is considered a food supplement. Preclinical studies in the murine model of active tuberculosis (TB) in the C3HeB/FeJ strain have demonstrated that daily administration of NR containing 10(3)-10(6)hkMn for 14days was able to stop the progression toward active TB [1]. The mechanism of action was linked to the induction of low dose tolerance and was related to the increase of Tuberculin Purified Protein Derivative (PPD) memory-specific Tregs (CD4(+)CD25(+)CD39(+) cells) after ex vivo incubation of splenocytes for 7days...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27989897/phenotypic-changes-of-peripheral-blood-mononuclear-cells-upon-corticosteroid-treatment-in-idiopathic-intermediate-uveitis
#17
Karoline Walscheid, Toni Weinhage, Dirk Foell, Carsten Heinz, Maren Kasper, Arnd Heiligenhaus
We analyzed phenotype and function of peripheral blood mononuclear cells in 9 patients with active idiopathic intermediate uveitis (IIU) before and after 6 and 12weeks of systemic corticosteroid (CS) treatment and compared to 28 healthy individuals. Monocytes from IIU patients showed increased MHCII expression compared with controls (p=0.09). Treatment reduced expression of MHCII, CD86, CD39 and CD124 (all p<0.05), whereas the percentage of CD121b-expressing monocytes was increased by week 6 (p=0.039). Patients showed alterations in T cell polarization (Th1/Th2 ratio: patients 5...
October 28, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27988461/divergent-regulatory-roles-of-extracellular-atp-in-the-degranulation-response-of-mouse-bone-marrow-derived-mast-cells
#18
Kazuki Yoshida, Masaaki Ito, Isao Matsuoka
Mast cells (MCs) play a critical role in allergic inflammation. Although purinergic signalling is implicated in the regulation of various immune responses, its role in MC function is not fully understood. In this study, we investigated the regulatory role of purinergic signalling in MC degranulation, using mouse bone marrow-derived mast cells (BMMCs). Notably, BMMCs expressed various functional P2 adenosine triphosphate (ATP) receptors, including ionotropic P2X4 and P2X7, involved in the regulation of BMMC degranulation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27930600/increased-frequency-of-cd39-cd56-bright-natural-killer-cells-in-hiv-1-infection-correlates-with-immune-activation-and-disease-progression
#19
Patrick Dierks, Raluca Wroblewski, Johanna M Eberhard, Gloria Martrus, Olaf Degen, Sandra Hertling, Stefan Schmiedel, Sebastian Lunemann, Anja Hüfner, Ansgar W Lohse, Marcus Altfeld, Jan van Lunzen, Julian Schulze Zur Wiesch
The expression pattern of the ectonucleotidases CD39 and CD73 on NK cells was examined in PBMC of 61 HIV-1 infected patients. Increased frequencies of CD39CD56 NK cells were detectable in untreated HIV patients, which was associated with high viral load, low CD4+ T cell count and CD8+ T cell activation. Additionally, levels of CD39 on NK cells were inducible by in vitro stimulation of NK cells, correlating with Aryl hydrocarbon receptor (AHR) and IL-10 expression. Here, we provide first evidence of increased CD39CD56 NK cell frequencies during HIV infection, which might have consequences for NK cell function and HIV pathogenesis...
December 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27906627/oxidized-low-density-lipoproteins-enhance-expression-and-activity-of-cd39-and-cd73-in-the-human-aortic-valve-endothelium
#20
Ewa Kaniewska-Bednarczuk, Michał Mielcarek, Adrian H Chester, Ewa M Slominska, Magdi H Yacoub, Ryszard T Smolenski
Extracellular nucleotides regulate thrombosis, inflammation, and immune response. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) convert extracellular nucleotides in a sequential order: ATP to ADP, AMP, and then to adenosine. In this study, we aimed to test an effect of oxidized low-density lipoprotein (ox-LDL) on CD39 and CD73 in endothelial cells. Human aortic valve endothelial cells were exposed to ox-LDL for 24-48 h. Next, the activity, protein expression, and mRNA transcripts level of CD39 and CD73 were characterized by an incubation with ATP or AMP followed by high-performance liquid chromatography analysis of media as well as western blots and qPCR...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
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