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https://www.readbyqxmd.com/read/28923439/peripheral-blood-monocytes-reveal-an-activated-phenotype-in-pediatric-uveitis
#1
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Dirk Holzinger, Carsten Heinz, Maren Kasper, Dirk Foell
OBJECTIVE: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU). METHODS: Peripheral blood monocytes from children with JIA (either with (n=18) or without uveitis (n=11)), idiopathic anterior uveitis (IAU; n=12) and healthy controls (n=11) were analyzed by flow cytometry. RESULTS: Percentage of CD14+CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups...
September 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28916770/changes-in-cd73-cd39-and-cd26-expression-on-t-lymphocytes-of-anca-associated-vasculitis-patients-suggest-impairment-in-adenosine-generation-and-turn-over
#3
Lovis Kling, Urs Benck, Annette Breedijk, Lisa Leikeim, Marianne Heitzmann, Stefan Porubsky, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Extracellular adenosine, generated via the concerted action of CD39 and CD73, contributes to T-cell differentiation and function. Adenosine concentrations are furthermore influenced by adenosine deaminase binding protein CD26. Because aberrant T-cell phenotypes had been reported in anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitis (AAV) patients, an impaired expression of these molecules on T-cells of AAV patients was hypothesized in the present study. While in AAV patients (n = 29) CD26 was increased on CD4(+) lymphocytes, CD39 and CD73 were generally reduced on patients' T-cells...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28857186/anti-schistosome-antibodies-change-ntpdase-1-activity-from-macrophages
#4
Danielle Gomes Marconato, Michélia Antônia do Nascimento Gusmão, Juliana Melo, Juciane Maria de Andrade Castro, Gilson Costa Macedo, Eveline Gomes Vasconcelos, Priscila de Faria-Pinto
NTPDases are enzymes that hydrolyze di- and tri-phosphate nucleosides, regulating purinergic signaling in many organisms. The Schistosoma mansoni NTPDases, SmATPDases 1 and 2 are antigenic proteins and display a significant homology with the isoforms found in mammalian cells. In this work, we investigated whether anti-SmATPDase antibodies from S. mansoni-infected mice sera show cross-reactivity with the NTPDase 1 isoform from macrophages and how this event affect the cell proliferation. By Western blot, anti-SmATPDase antibodies present in serum from infected mice recognized two bands with approximately 53 and 58 kDa, corresponding to NTPDase 1...
August 30, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28844316/identifying-early-pathogenic-events-during-vascular-calcification-in-uremic-rats
#5
Luis Hortells, Cecilia Sosa, Natalia Guillén, Susana Lucea, Ángel Millán, Víctor Sorribas
Vascular calcification in chronic kidney disease is a very complex process traditionally explained in multifactorial terms. Here we sought to clarify relevance of the diverse agents acting on vascular calcification in uremic rats and distinguish between initiating and complicating factors. After 5/6 nephrectomy, rats were fed a 1.2% phosphorus diet and analyzed at different time points. The earliest changes observed in the aortic wall were noticed 11 weeks after nephrectomy: increased Wnt inhibitor Dkk1 mRNA expression and tissue non-specific alkaline phosphatase (TNAP) expression and activity...
August 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28835242/granulocytic-myeloid-derived-suppressor-cells-suppress-virus-specific-cd8-t-cell-responses-during-acute-friend-retrovirus-infection
#6
Malgorzata Drabczyk-Pluta, Tanja Werner, Daniel Hoffmann, Qibin Leng, Lieping Chen, Ulf Dittmer, Gennadiy Zelinskyy
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases. Previously these suppressive cells were observed to expand in HIV patients and in a mouse retrovirus model, yet their suppressive effect on virus-specific CD8(+) T cells in vitro and in vivo has not been characterized thus far. RESULTS: We used the Friend retrovirus (FV) model to demonstrate that MDSCs expand and become activated during the late phase of acute FV infection...
August 23, 2017: Retrovirology
https://www.readbyqxmd.com/read/28801624/stingray-venom-activates-il-33-producing-cardiomyocytes-but-not-mast-cell-to-promote-acute-neutrophil-mediated-injury
#7
Janaina Cardoso Dos Santos, Lidiane Zito Grund, Carla Simone Seibert, Elineide Eugênio Marques, Anderson Brito Soares, Valerie F Quesniaux, Bernhard Ryffel, Monica Lopes-Ferreira, Carla Lima
One of the hallmarks of acute inflammation is neutrophil infiltration of tissues. We investigated molecular mechanisms implicated in acute neutrophilic inflammation induced by the venom of a freshwater stingray (Potamotrygon cf. henlei) in mice. Ray venom induced early mobilization of neutrophil in the microvasculature of cremaster mice and infiltration of the peritoneal cavity 2 hours after injury, in a dose-response manner. IL-1β, IL-6, TNF-α, and KC were produced. The neutrophilic infiltration did not occur in mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and p38 MAPK signaling blocked...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759073/defective-atp-breakdown-activity-related-to-an-entpd1-gene-mutation-demonstrated-using-31-p-nmr-spectroscopy
#8
Atara Nardi-Schreiber, Gal Sapir, Ayelet Gamliel, Or Kakhlon, Jacob Sosna, J Moshe Gomori, Vardiella Meiner, Alexander Lossos, Rachel Katz-Brull
The ecto-nucleoside triphosphate diphosphohydrolase-1 (E-NTPDase-1, CD39) enzyme is responsible for the breakdown of extracellular ATP to ADP and then to AMP by a two-step process. Defective CD39 activity has been described in a variety of medical conditions including malignancy and rheumatic diseases and has been proved to be of major diagnostic and clinical importance. Here we show for the first time that a (31)P NMR spectroscopy methodology enables the quantification of these two steps in a single blood sample...
July 31, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28751543/adpase-cd39-fused-to-glycoprotein-vi-fc-boosts-local-antithrombotic-effects-at-vascular-lesions
#9
Heidrun Degen, Oliver Borst, Melanie Ziegler, Ann-Katrin Mojica Munoz, Janina Jamasbi, Britta Walker, Silvia Göbel, Julia Fassbender, Kristin Adler, Richard Brandl, Götz Münch, Reinhard Lorenz, Wolfgang Siess, Meinrad Gawaz, Martin Ungerer
BACKGROUND: GPVI (Glycoprotein VI) is the essential platelet collagen receptor in atherothrombosis. Dimeric GPVI-Fc (Revacept) binds to GPVI binding sites on plaque collagen. As expected, it did not increase bleeding in clinical studies. GPVI-Fc is a potent inhibitor of atherosclerotic plaque-induced platelet aggregation at high shear flow, but its inhibition at low shear flow is limited. We sought to increase the platelet inhibitory potential by fusing GPVI-Fc to the ectonucleotidase CD39 (fusion protein GPVI-CD39), which inhibits local ADP accumulation at vascular plaques, and thus to create a lesion-directed dual antiplatelet therapy that is expected to lack systemic bleeding risks...
July 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28749465/acid-sphingomyelinase-mediates-human-cd4-t-cell-signaling-potential-roles-in-t-cell-responses-and-diseases
#10
REVIEW
Aiping Bai, Yuan Guo
Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had been reported to have an important role in regulating immune cell functions inclusive of macrophages, NK cells, and CD8(+) T cells, whereas the role of ASM bioactivity in regulation of human CD4(+) T-cell functions remained uncertain. Recent studies have provided novel findings in this field. Upon stimulation of CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular downstream signal cascades of CD3 and CD28, and regulates CD4(+) T-cell activation and proliferation...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28743609/expression-of-cd73-slows-down-migration-of-skin-dendritic-cells-affecting-the-sensitization-phase-of-contact-hypersensitivity-reactions-in-mice
#11
A Neuberger, S Ring, C Silva-Vilches, J Schrader, A Enk, K Mahnke
BACKGROUND: Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. OBJECTIVE: To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene (TNCB) induced CHS reactions...
July 9, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28742222/disruption-of-the-atp-adenosine-balance-in-cd39-mice-is-associated-with-handling-induced-seizures
#12
Amanda J Lanser, Rafael M Rezende, Stephen Rubino, Paul J Lorello, Dustin J Donnelly, Huixin Xu, Lauren A Lau, Chris G Dulla, Barbara J Caldarone, Simon C Robson, Howard L Weiner
Seizures are due to excessive, synchronous neuronal firing in the brain and are characteristic of epilepsy, the fourth most prevalent neurologic disease. Herein, we report handling-induced and spontaneous seizures in mice deficient of CD39, a cell-surface ATPase highly expressed on microglial cells. CD39(-/-) mice with handling-induced seizures had normal input-output curves and paired-pulse ratio measured from hippocampal slices and lacked microgliosis, astrogliosis or overt cell loss in the hippocampus and cortex...
July 25, 2017: Immunology
https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#13
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28690614/what-else-can-cd39-tell-us
#14
REVIEW
Hai Zhao, Cong Bo, Yan Kang, Hong Li
As the rate-limiting enzyme in ATP/ADP-AMP-adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39(hi) Tregs, but not CD25(hi) Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28683106/cytomegalovirus-infection-in-hiv-infected-and-uninfected-individuals-is-characterized-by-circulating-regulatory-t-cells-of-unconstrained-antigenic-specificity
#15
Adriana Tovar-Salazar, Adriana Weinberg
Cytomegalovirus (CMV) infection is associated with immune-suppression in immune-compromised hosts and old adults. We previously showed that ex vivo CMV restimulation of peripheral blood mononuclear cells (PBMC) of CMV-seropositive volunteers expanded CD4+CD27-CD28- regulatory T cells (Tregs). Here we evaluate the phenotype and function of circulating CD4+CD27-CD28- T cells of CMV-seropositive adults. Compared with CMV-seronegative, CMV-seropositive adults had 10-fold higher CD4+CD27-CD28-% T cells in PBMC. Circulating CD4+CD27-CD28- T cells from both CMV-seropositive and seronegative donors expressed higher levels of TGFβ, granzyme B, CD39, CD147 and IL-35, and lower levels of CD127, compared with their parent circulating CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28680754/cd39-cd73-upregulation-on-myeloid-derived-suppressor-cells-via-tgf-%C3%AE-mtor-hif-1-signaling-in-patients-with-non-small-cell-lung-cancer
#16
Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Yu Ping, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Li Yang, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo Huang, Bin Zhang, Yi Zhang
CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b(+)CD33(+) myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679740/role-of-adp-receptors-on-platelets-in-the-growth-of-ovarian-cancer
#17
Min Soon Cho, Kyunghee Noh, Monika Haemmerle, Dan Li, Hyun Park, Qianghua Hu, Takeshi Hisamatsu, Takashi Mitamura, Sze Ling Celia Mak, Satya Kunapuli, Qing Ma, Anil K Sood, Vahid Afshar-Kharghan
We investigated the effect of platelets on ovarian cancer, and role of ADP receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, P2Y12 inhibitor (Ticagrelor) reduced tumor growth by 60% compared to aspirin and 75% compared to placebo. In P2Y12(-/-) mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared to WT mice. On the other hand, there was no difference in the tumor growth between P2Y1(-/-) and WT mice...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#18
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28658673/hyperthermia-and-associated-changes-in-membrane-fluidity-potentiate-p2x7-activation-to-promote-tumor-cell-death
#19
Paola de Andrade Mello, Shu Bian, Luiz Eduardo Baggio Savio, Haohai Zhang, Jingping Zhang, Wolfgang Junger, Márcia Rosângela Wink, Guido Lenz, Andréia Buffon, Yan Wu, Simon Christopher Robson
Extracellular ATP (eATP) accumulation within the tumor microenvironment (TME) has the potential to activate purinergic signaling. The eATP evoked signaling effects bolster antitumor immune responses while exerting direct cytotoxicity on tumor cells and vascular endothelial cells, mediated at least in part through P2X7 receptors. Approaches to augment purinergic signaling in TME e.g. by ectonucleotidase CD39 blockade, and/or boosting P2X7 functional responses, might be used as immunomodulatory therapies in cancer treatment...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28658271/regulatory-t-cell-frequencies-and-phenotypes-following-anti-viral-vaccination
#20
A Charlotte M T de Wolf, Susan van Aalst, Irene S Ludwig, Caroline L Bodinham, David J Lewis, Ruurd van der Zee, Willem van Eden, Femke Broere
Regulatory T cells (Treg) function in the prevention of excessive inflammation and maintenance of immunological homeostasis. However, these cells may also interfere with resolution of infections or with immune reactions following vaccination. Effects of Treg on vaccine responses are nowadays investigated, but the impact of vaccination on Treg homeostasis is still largely unknown. This may be a relevant safety aspect, since loss of tolerance through reduced Treg may trigger autoimmunity. In exploratory clinical trials, healthy adults were vaccinated with an influenza subunit vaccine plus or minus the adjuvant MF59®, an adjuvanted hepatitis B subunit vaccine or a live attenuated yellow fever vaccine...
2017: PloS One
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