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https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#1
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28414024/novel-high-throughput-cell-based-hybridoma-screening-methodology-using-the-celigo-image-cytometer
#2
Haohai Zhang, Leo Li-Ying Chan, William Rice, Nasim Kassam, Maria Serena Longhi, Haitao Zhao, Simon C Robson, Wenda Gao, Yan Wu
Hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. Technical issues associated with ELISA- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. Conventional ELISA screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain protein complexes...
April 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#3
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387597/human-cd39-treg-cells-express-th17-associated-surface-markers-and-suppress-il-17-via-a-stat3-dependent-mechanism
#4
Jessica R Magid-Bernstein, Christine M Rohowsky-Kochan
Human CD4(+) T regulatory cells (Tregs) are a population of phenotypically and functionally diverse cells that downregulate inflammatory and autoimmune responses. As Th17 cells play an important role in the pathogenesis of autoimmune diseases, it is critical to elucidate the mechanisms regulating these cells. In this study, we examined the molecular basis underlying the phenotypic and functional diversity of human Tregs expressing the ectonucleotidase CD39. CD4(+)CD25(hi)CD39(+) Tregs inhibit the proliferative response and the secretion of IL-17 and IFN-γ of autologous CD4(+) T effector cells, while CD4(+)CD25(hi)CD39(-) Tregs only suppress IFN-γ production...
April 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28383711/synergistic-effect-of-regulatory-t-cells-and-proinflammatory-cytokines-in-angiogenesis-in-the-endometriotic-milieu
#5
Xiao-Qiu Wang, Wen-Jie Zhou, Xue-Zhen Luo, Yu Tao, Da-Jin Li
STUDY QUESTION: Do regulatory T cells (Tregs) contribute to angiogenesis in endometriosis? SUMMARY ANSWER: High levels of CCL17 and CCL22 cause the recruitment of Tregs, upregulate the immunosuppression of Tregs and, in turn, may promote angiogenesis in endometrial cells in synergy with proinflammatory cytokines. WHAT IS ALREADY KNOWN: The peritoneal fluid of patients with endometriosis has a higher percentage of Tregs than that of normal individuals; however, the regulatory role of Tregs in the disease remains unclear...
April 4, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#6
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28376099/the-adenosine-generating-enzymes-cd39-cd73-control-microglial-processes-ramification-in-the-mouse-brain
#7
Marina Matyash, Oleksandr Zabiegalov, Stefan Wendt, Vitali Matyash, Helmut Kettenmann
Microglial cells invade the brain as amoeboid precursors and acquire a highly ramified morphology in the postnatal brain. Microglia express all essential purinergic elements such as receptors, nucleoside transporters and ecto-enzymes, including CD39 (NTPDase1) and CD73 (5'-nucleotidase), which sequentially degrade extracellular ATP to adenosine. Here, we show that constitutive deletion of CD39 and CD73 or both caused an inhibition of the microglia ramified phenotype in the brain with a reduction in the length of processes, branching frequency and number of intersections with Sholl spheres...
2017: PloS One
https://www.readbyqxmd.com/read/28375551/phenotypic-characterization-of-regulatory-t-cells-from-antiretroviral-na%C3%A3-ve-hiv-1-infected-people
#8
Georgia N Ambada, Claudine E Ntsama, Nadesh N Nji, Loveline N Ngu, Sake N Carole, Abel Lissom, Flaurent T Tchouangeu, Jules Tchadji, Martin Sosso, François-Xavier Etoa, Godwin W Nchinda
Regulatory T cells (Tregs) play a key role in dampening excessive immune activation. However antiretroviral (ARV) naive HIV-1 infection maintains the immune system in a sustained state of activation that could alter both Tregs surface markers and functions. Since Tregs surface markers are directly linked to their functions the overall objective of this study was to determine how ARV naïve HIV infection affects the phenotypic properties of Tregs. Our data showed that in ARV naive HIV-1 infection, Tregs are dominated by effector (CD45RA(+) CD27(-) CCR7(-) CD62L(-) ) and effector memory (CD45RA(-) CD27(-) CCR7(-) CD62L(-) ) cells...
April 4, 2017: Immunology
https://www.readbyqxmd.com/read/28373875/roles-and-modalities-of-ectonucleotidases-in-remodeling-the-multiple-myeloma-niche
#9
Antonella Chillemi, Valeria Quarona, Luca Antonioli, Davide Ferrari, Alberto L Horenstein, Fabio Malavasi
Ectoenzymes are cell surface molecules, which represent functional bridges between the environment and the cytoplasm. One set of ectoenzymes-CD39, CD38, CD203a, and CD73-leads to the generation of adenosine (ADO) by metabolizing ATP and NAD(+). While ADO is known to control inflammation and suppress immune responses, other aspects of ADO function are still obscure, mainly due to its short half-life in biological fluids. Human multiple myeloma (MM) grows in the closed system of the bone marrow (BM) niche representing an ideal setting for studying ectoenzymes and their products...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28349869/modulation-of-regulatory-t-cells-by-intranasal-allergen-immunotherapy-in-an-experimental-rat-model-of-airway-allergy
#10
Saibal Moitra, Ankur Datta, Somnath Mondal, Iman Hazra, Sk Md Omar Faruk, Prasanta K Das, Anjan K Basu, Santanu K Tripathi, Swapna Chaudhuri
Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients...
March 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28346024/increased-il-4-and-il-17-producing-cd8-cells-are-related-to-decreased-cd39-cd4-foxp3-cells-in-allergic-asthma
#11
Li Ping, Zhen Yang, Qin Zhang, Wei Wang, Jiong Yang
OBJECTIVE: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen primed CD8(+) T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8(+) T cells and CD39(+) Tregs. METHODS: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i...
March 27, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28344891/tumor-infiltrating-cd39-%C3%AE-%C3%AE-tregs-are-novel-immunosuppressive-t-cells-in-human-colorectal-cancer
#12
Guoming Hu, Pin Wu, Pu Cheng, Zhigang Zhang, Zhen Wang, Xiuyan Yu, Xuan Shao, Dang Wu, Jun Ye, Tao Zhang, Xiaochen Wang, Fuming Qiu, Jun Yan, Jian Huang
Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39(+) γδTreg in human colorectal cancer (CRC). CD39(+) γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4(+) or CD8(+) Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344879/prostaglandin-e2-mediated-adenosinergic-effects-on-cd14-cells-self-amplifying-immunosuppression-in-cancer
#13
Saly Al-Taei, Josephine Salimu, Lisa K Spary, Aled Clayton, Jason F Lester, Zsuzsanna Tabi
CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE- or blood-derived CD14(+) cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28343356/development-of-a-novel-strategy-to-target-cd39-antithrombotic-activity-to-the-endothelial-platelet-microenvironment-in-kidney-ischemia-reperfusion-injury
#14
Maithili Sashindranath, Karen M Dwyer, Shala Dezfouli, Carly Selan, Sandra Crikis, Bo Lu, Yuping Yuan, Michael J Hickey, Karlheinz Peter, Simon C Robson, Peter J Cowan, Harshal H Nandurkar
Kidney ischemia-reperfusion injury (IRI) is common during transplantation. IRI is characterised by inflammation and thrombosis and associated with acute and chronic graft dysfunction. P-selectin and its ligand PSGL-1 are cell adhesion molecules that control leukocyte-endothelial and leukocyte-platelet interactions under inflammatory conditions. CD39 is the dominant vascular nucleotidase that facilitates adenosine generation via extracellular ATP/ADP-phosphohydrolysis. Adenosine signalling is protective in renal IRI, but CD39 catalytic activity is lost with exposure to oxidant stress...
March 25, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28302652/the-entpd1-promoter-polymorphism-860-a-g-rs3814159-is-associated-with-increased-gene-transcription-protein-expression-cd39-ntpdase1-enzymatic-activity-and-thromboembolism-risk
#15
James P Maloney, Brian R Branchford, Gary L Brodsky, Maxwell S Cosmic, David W Calabrese, Christina L Aquilante, Kelly W Maloney, Joseph R Gonzalez, Weiming Zhang, Kerrie L Moreau, Kerri L Wiggins, Nicholas L Smith, Ulrich Broeckel, Jorge Di Paola
Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1) degrades the purines ATP and ADP that are key regulators of inflammation and clotting. We hypothesized that NTPDase1 polymorphisms exist and that they regulate this pathway. We sequenced the ENTPD1 gene (encoding NTPDase1) in 216 subjects then assessed genotypes in 2 cohorts comprising 2213 humans to identify ENTPD1 polymorphisms associated with venous thromboembolism (VTE). The G allele of the intron 1 polymorphism rs3176891 was more common in VTE vs...
March 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28301515/il-22-gm-csf-and-il-17-in-peripheral-cd4-t-cell-subpopulations-during-multiple-sclerosis-relapses-and-remission-impact-of-corticosteroid-therapy
#16
Nathalie Muls, Zakia Nasr, Hong Anh Dang, Christian Sindic, Vincent van Pesch
Multiple sclerosis (MS) is thought to be a Th17-mediated dysimmune disease of the central nervous system. However, recent publications have questioned the pathogenicity of IL-17 per se and rather suggest the implication of other Th17-related inflammatory mediators. Therefore, we studied the expression of GM-CSF, IL-22, IL-24, IL-26 and CD39 in peripheral blood mononuclear cells (PBMCs) from MS patients during relapses, remission and following corticosteroid treatment. We performed qPCR to measure mRNA levels from ex vivo or in vitro-stimulated PBMCs...
2017: PloS One
https://www.readbyqxmd.com/read/28295154/phenotypical-analysis-of-ectoenzymes-cd39-cd73-and-adenosine-receptor-2a-in-cd4-cd25-high-foxp3-regulatory-t-cells-in-psoriasis
#17
Ling Han, Hideaki Sugiyama, Qi Zhang, Kexiang Yan, Xu Fang, Thomas S McCormick, Kevin D Cooper, Qiong Huang
BACKGROUND: CD39 and CD73 are two novel cell surface markers of CD25(high) Foxp3(+) regulatory T-cells (Tregs). Concordant expression of these two ectoenzymes not only discriminate Tregs from other cell populations, but also generates pericellular adenosine, which has been reported to suppress proliferation of activated T effector (Teff) cells. Because it is currently unclear whether human ectoenzymes (CD39/CD73) are involved in the impaired suppressive activity of Tregs in psoriasis, we examined the frequencies and phenotypes of CD39/CD73-expressing Tregs and related receptor adenosine receptor 2A (A2A R) in peripheral blood of patients with different types of psoriasis...
March 15, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28288184/cd73-is-expressed-by-inflammatory-th17-cells-in-experimental-autoimmune-encephalomyelitis-but-does-not-limit-differentiation-or-pathogenesis
#18
Gerard Hernandez-Mir, Mandy J McGeachy
CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine, thus inhibiting inflammation. TGFβ-mediated CD73 expression on 'regulatory' Th17 cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be inflammatory in Crohn's disease. CD73 has previously been reported to contribute to inflammation in the central nervous system (CNS). In experimental autoimmune encephalomyelitis (EAE), we found that inflammatory cytokine-producing Th17 cells showed increased CD73 expression as disease progressed...
2017: PloS One
https://www.readbyqxmd.com/read/28283419/circulating-gluten-specific-foxp3-cd39-regulatory-t-cells-have-impaired-suppressive-function-in-celiac-disease
#19
Laura Cook, C Mee Ling Munier, Nabila Seddiki, David van Bockel, Noé Ontiveros, Melinda Y Hardy, Jana K Gillies, Megan K Levings, Hugh Reid, Jan Peterson, Jamie Rossjohn, Robert P Anderson, John Zaunders, Jason A Tye-Din, Anthony D Kelleher
BACKGROUND: Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in celiac disease has been well characterized, the role of regulatory T-cells (Tregs) in the loss of tolerance to gluten remains poorly understood. OBJECTIVE: To define if celiac disease patients have a dysfunction or lack of gluten-specific FOXP3(+) Tregs. METHODS: Treated celiac disease patients underwent oral wheat challenge to stimulate re-circulation of gluten-specific T-cells...
March 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28258700/the-ectonucleotidases-cd39-and-cd73-novel-checkpoint-inhibitor-targets
#20
REVIEW
Bertrand Allard, Maria Serena Longhi, Simon C Robson, John Stagg
Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are newly developing interventions that modify the patient's immune system to fight cancer, by either directly stimulating rejection-type processes or blocking suppressive pathways. Extracellular adenosine generated by the ectonucleotidases CD39 and CD73 is a newly recognized "immune checkpoint mediator" that interferes with anti-tumor immune responses...
March 2017: Immunological Reviews
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