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https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#1
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28509416/the-importance-of-cd39-cd43-cd81-and-cd95-expression-for-differentiating-b-cell-lymphoma-by-flow-cytometry
#2
Chandra Chiappin Cardoso, Mariangeles Auat, Iris Mattos Santos-Pirath, Renata Cristina Messores Rudolf-Oliveira, Jessica Pires da Silva, Bárbara Gil Lange, Danielle Siegel, Ana Carolina Rabello de Moraes, Joanita Angela Gonzaga Del Moral, Maria Claudia Santos-Silva
BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a combination of morphology, immunophenotype, recurrent cytogenetic aberration and clinical features. However, even with these diagnostic tools, a definitive diagnosis can be difficult to achieve. Therefore, the aim of this study was to assess the profile of CD39, CD43, CD81 and CD95 expression in diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt lymphoma (BL) cases. METHODS: To address this issue, we investigated the expression of CD39, CD43, CD81 and CD95 by eight-color flow cytometry in retrospective cases from 2014 to 2016...
May 16, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#3
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28487695/regulatory-t-cells-and-pro-inflammatory-responses-predominate-in-children-with-tuberculosis
#4
Elizabeth Whittaker, Mark Nicol, Heather J Zar, Beate Kampmann
BACKGROUND: Following infection with Mycobacterium tuberculosis (M.tb), children are more susceptible to develop disease particularly extrapulmonary disease than adults. The exact mechanisms required for containment of M.tb are not known, but would be important to identify correlates of protection. OBJECTIVE: To comprehensively analyze key immune responses to mycobacteria between HIV-negative children with extrapulmonary TB (EPTB) compared to children with pulmonary TB (PTB) or healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28487312/complete-deletion-of-cd39-is-atheroprotective-in-apolipoprotein-e-deficient-mice
#5
Marco De Giorgi, Keiichi Enjyoji, Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Richard J Gumina, Ryszard T Smolenski, Simon C Robson
CD39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of CD39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE-/-) and Cd39/ApoE double knockout (Cd39-/-/ApoE-/-, DKO) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly less atherosclerotic lesions than ApoE KO mice, irrespective of diet...
May 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28472483/a-single-chain-antibody-cd39-fusion-protein-targeting-activated-platelets-protects-from-cardiac-ischaemia-reperfusion-injury
#6
Melanie Ziegler, Jan David Hohmann, Amy Kate Searle, Meike-Kristin Abraham, Harshal H Nandurkar, Xiaowei Wang, Karlheinz Peter
Aims: CD39 is a cell membrane NTPase with anti-inflammatory and anti-platelet effects. However, its clinical use is limited by its bleeding side effect. With the goal of harnessing its therapeutic potential while avoiding haemostatic problems, we designed a fusion protein consisting of the extracellular domain of CD39 and a single-chain antibody (Targ-CD39) that specifically binds to activated glycoprotein (GP)IIb/IIIa and thus to activated platelets. Through this enrichment at activated platelets, the required systemic dose is below the dose impairing haemostasis...
May 2, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28469075/bilirubin-suppresses-th17-immunity-in-colitis-by-upregulating-cd39
#7
Maria Serena Longhi, Marta Vuerich, Alireza Kalbasi, Jessica E Kenison, Ada Yeste, Eva Csizmadia, Byron Vaughn, Linda Feldbrugge, Shuji Mitshuhashi, Barbara Wegiel, Leo Otterbein, Alan Moss, Francisco J Quintana, Simon C Robson
Unconjugated bilirubin (UCB), a product of heme oxidation, has known immunosuppressant properties but the molecular mechanisms, other than antioxidant effects, remain largely unexplored. We note that UCB modulates T helper type 17 (Th17) immune responses, in a manner dependent upon heightened expression of CD39 ectonucleotidase. UCB has protective effects in experimental colitis, where it enhances recovery after injury and preferentially boosts IL-10 production by colonic intraepithelial CD4+ cells. In vitro, UCB confers immunoregulatory properties on human control Th17 cells, as reflected by increased levels of FOXP3 and CD39 with heightened cellular suppressor ability...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28462511/altered-expression-of-enos-prostacyclin-synthase-prostaglandin-g-h-synthase-and-thromboxane-synthase-in-porcine-aortic-endothelial-cells-after-exposure-to-human-serum-relevance-to-xenotransplantation
#8
Pengfei Chen, Hanchao Gao, Ying Lu, Huirong Nie, Zhaoming Liu, Yu Zhao, Nana Fan, Qingjian Zou, Yifan Dai, Aifa Tang, Hidetaka Hara, Zhiming Cai, David K C Cooper, Liangxue Lai, Lisha Mou
Under normal conditions, the activity of platelets is stringently and precisely balanced between activation and quiescent state. This guarantees rapid hemostasis and avoids uncontrolled thrombosis. However, excessive platelet activation and resulting thrombotic microangiopathy are frequently observed in pig-to-primate xenotransplantation models. Endothelium-derived inhibitory mechanisms play an important role in regulation of platelet activation. These mainly include nitric oxide (NO), prostacyclin PGI2 and adenosine, which are synthesized by endothelial nitric oxide synthases (eNOS), prostacyclin synthase, and CD39/CD73, respectively...
April 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#9
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
#10
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
#11
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...
May 16, 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
#12
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
#13
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...
June 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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