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https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#1
Linda Feldbrügge, Z Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Stephanie Tran, Eric U Yee, Sonja Rothweiler, Kahini A Vaid, Jean Sévigny, Moritz Schmelzle, Yury V Popov, Simon C Robson
Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice...
November 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29127315/human-gingiva-derived-mesenchymal-stem-cells-ameliorate-streptozoticin-induced-t1dm-in-mice-via-suppression-of-t-effector-cells-and-up-regulating-treg-subsets
#2
Wei Zhang, Li Zhou, Junlong Dang, Ximei Zhang, Julie Wang, Yanming Chen, Jichao Liang, Dongqing Li, Jilin Ma, Jia Yuan, Weiwen Chen, Homayoun H Zadeh, Nancy Olsen, Song Guo Zheng
There is yet no cure for type 1 diabetes (T1DM) so far. A significant body of evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) showed great potential in controlling T1DM. But there exists much difficulty in using BMSCs as a clinical therapy. We here test whether a new population of mesenchymal stem cells from human gingiva (GMSCs), which has many advantages over BMSCs, can delay or prevent progress of T1DM. GMSCs were adoptively transferred to multiple low-dose streptozotocin (STZ)-induced T1DM...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126851/ccr6-signaling-inhibits-suppressor-function-of-induced-treg-during-gut-inflammation
#3
Neeraja Kulkarni, Heikrujam Thoihen Meitei, Sandip Ashok Sonar, Praveen Kumar Sharma, Vikkarasan Rehman Mujeeb, Sharad Srivastava, Ramanamurthy Boppana, Girdhari Lal
CCR6 is a G protein-coupled receptor (GPCR) that binds to a specific chemokine, CCL20. The role of CCR6-CCL20 is very well studied in the migration of immune cells, but the non-chemotaxis functions of CCR6 signaling were not known. Here, we show that during gut inflammation, the frequency of Foxp3(+)CD4(+) T cells (Tregs) reduced in the secondary lymphoid tissues and CCR6(+) Tregs enhanced the expression of RORγt. The peripheral blood mononuclear cells (PBMCs) of ulcerative colitis (UC) patients showed lower percentages of Foxp3(+)CD4(+) T cells, as compared to healthy individuals, with CCR6(+) Tregs showing higher RORγt expression as compared to CCR6(-)Tregs...
November 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29108754/extracellular-adenosine-produced-by-ecto-5-nucleotidase-cd73-regulates-macrophage-pro-inflammatory-responses-nitric-oxide-production-and-favors-salmonella-persistence
#4
Matthew G Costales, Mohammad Samiul Alam, Christopher Cavanaugh, Kristina M Williams
Surface enzymes CD39 (nucleoside triphosphate dephosphorylase) and CD73 (ecto-5'-nucleotidase) mediate the synthesis of extracellular adenosine that can regulate immune responses. Adenosine produced by CD39/CD73 acts via adenosine receptors (ARs). CD73 is expressed by a variety of cell types and mediates anti-inflammatory responses. Because efficient innate immune responses are required for clearance of Salmonella infection, we investigated the role of CD73 in macrophage function, including phagocytosis, intracellular killing of Salmonella, and anti-bacterial pro-inflammatory responses to Salmonella-whole cell lysate (ST-WCL) or Salmonella infection...
November 11, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29103803/cd39-and-cd73-activity-are-protective-in-a-mouse-model-of-antiphospholipid-antibody-induced-miscarriages
#5
Anushka N Samudra, Karen M Dwyer, Carly Selan, Susanna Freddi, Lisa Murray-Segal, Mandana Nikpour, Michael J Hickey, Karlheinz Peter, Simon C Robson, Maithili Sashindranath, Peter J Cowan, Harshal H Nandurkar
OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder of young adults associated with devastating pregnancy complications (recurrent miscarriages, preeclampsia and low birth weight) and vascular complications including thrombosis. The key components implicated in pathogenesis of APS are the complement cascade and tissue factor (TF) activity causing inflammation and coagulation. Purinergic signalling involving catabolism of ATP to adenosine by cell-surface enzymes CD39 and CD73 has anti-inflammatory and anti-thrombotic effects...
November 2, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29103633/cd8-cd28-cd127-lo-cd39-regulatory-t-cell-expansion-a%C3%A2-new-possible-pathogenic-mechanism-for-hiv-infection
#6
Daniela Fenoglio, Chiara Dentone, Alessio Signori, Antonio Di Biagio, Alessia Parodi, Francesca Kalli, Giorgia Nasi, Monica Curto, Giovanni Cenderello, Pasqualina De Leo, Valentina Bartolacci, Giancarlo Orofino, Laura Ambra Nicolini, Lucia Taramasso, Edoardo Fiorillo, Valeria Orrù, Paolo Traverso, Bianca Bruzzone, Federico Ivaldi, Eugenio Mantia, Michele Guerra, Simone Negrini, Mauro Giacomini, Sanjay Bhagani, Gilberto Filaci
BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4(+) T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4(+) T cells/μL. CD8(+)CD28(-)CD127(lo)CD39(+) T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8(+)CD28(-)CD127(lo)CD39(+) Treg cells in the circulation of HIV-infected patients...
October 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29090621/post-thyroidectomy-hypothyroidism-increases-the-expression-and-activity-of-ectonucleotidases-in-platelets-possible-involvement-of-reactive-oxygen-species
#7
Jucimara Baldissarelli, Micheli M Pillat, Roberta Schmatz, Andréia M Cardoso, Fátima H Abdalla, Juliana S de Oliveira, Carla R N Polachini, Emerson Casali, Clarissa Pereira Bornemann, Henning Ulrich, Vera M Morsch, Maria R C Schetinger
Signaling mediated by purines is a widespread mechanism of cell-cell communication related to vasomotor responses and the control of platelet function in the vascular system. However, little is known about the involvement of this signaling as well as the role of reactive oxygen species (ROS) in the development of hypothyroidism. Therefore, the present study investigates changes in the purinergic system, including enzyme activities and expression in platelets, and oxidative profiles in patients with post-thyroidectomy hypothyroidism...
November 1, 2017: Platelets
https://www.readbyqxmd.com/read/29083399/oxidative-stress-controls-regulatory-t-cell-apoptosis-and-suppressor-activity-and-pd-l1-blockade-resistance-in-tumor
#8
Tomasz Maj, Wei Wang, Joel Crespo, Hongjuan Zhang, Weimin Wang, Shuang Wei, Lili Zhao, Linda Vatan, Irene Shao, Wojciech Szeliga, Costas Lyssiotis, J Rebecca Liu, Ilona Kryczek, Weiping Zou
Live regulatory T cells (Treg cells) suppress antitumor immunity, but how Treg cells behave in the metabolically abnormal tumor microenvironment remains unknown. Here we show that tumor Treg cells undergo apoptosis, and such apoptotic Treg cells abolish spontaneous and PD-L1-blockade-mediated antitumor T cell immunity. Biochemical and functional analyses show that adenosine, but not typical suppressive factors such as PD-L1, CTLA-4, TGF-β, IL-35, and IL-10, contributes to apoptotic Treg-cell-mediated immunosuppression...
October 30, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29081352/development-of-the-hyaloid-choroidal-and-retinal-vasculatures-in-the-fetal-human-eye
#9
REVIEW
Gerard A Lutty, D Scott McLeod
The development of the ocular vasculatures is perfectly synchronized to provide the nutritional and oxygen requirements of the forming human eye. The fetal vasculature of vitreous, which includes the hyaloid vasculature, vasa hyaloidea propria, and tunica vasculosa lentis, initially develops around 4-6 weeks gestation (WG) by hemo-vasculogenesis (development of blood and blood vessels from a common progenitor, the hemangioblast). This transient fetal vasculature expands around 12 WG by angiogenesis (budding from primordial vessels) and remains until a retinal vasculature begins to form...
November 1, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/29071184/nanoliposomes-for-safe-and-efficient-therapeutic-mrna-delivery-a-step-toward-nanotheranostics-in-inflammatory-and-cardiovascular-diseases-as-well-as-cancer
#10
Meike-Kristin Abraham, Karlheinz Peter, Tatjana Michel, Hans Peter Wendel, Stefanie Krajewski, Xiaowei Wang
Rationale: Genetic therapy using modified mRNA for specific therapeutic protein expression for disease treatment and vaccination represents a new field of therapeutic and diagnostic medicine. Non-viral vectors transfection using biocompatible nanoliposomes enables safe and efficient delivery of therapeutic mRNA. Objective: Generation of non-toxic, cell-compatible cationic nanoliposomes as nanotheranostic agents to successfully deliver therapeutic mRNA. Methods and results: Cationic nanoliposomes (DC-Cholesterol/DOPE) were generated as transfection vehicles for either eGFP mRNA or the therapeutic anti-inflammatory, CD39 mRNA...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29069643/-repair-treg-cells-in-tissue-injury
#11
Chaoqi Zhang, Lifeng Li, Kexin Feng, Daoyang Fan, Wenhua Xue, Jingli Lu
Studies in mice and humans have elucidated an important role for Tregs in promoting tissue repair and restoring tissue integrity. Emerging evidence has revealed that Tregs promoted wound healing and repair processes at multiple tissue sites, such as the heart, liver, kidney, muscle, lung, bone and central nervous system. The localization of repair Tregs in the lung, muscle and liver exhibited unique phenotypes and functions. Epidermal growth factor receptor, amphiregulin, CD73/CD39 and keratinocyte growth factor are important repair factors that are produced or expressed by repair Tregs; these factors coordinate with parenchymal cells to limit injury and promote repair...
October 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29066514/cd39-expression-defines-cell-exhaustion-in-tumor-infiltrating-cd8-t-cells
#12
Fernando P Canale, Maria C Ramello, Nicolas Núñez, Cintia L Araujo Furlan, Sabrina N Bossio, Melisa Gorosito Serrán, Jimena Tosello Boari, Andrés Del Castillo, Marta Ledesma, Christine Sedlik, Eliane Piaggio, Adriana Gruppi, Eva V Acosta Rodríguez, Carolina L Montes
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL-2 and expression of co-inhibitory receptors...
October 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/29066254/ci8-short-a-novel-lps-induced-peptide-from-the-ascidian-ciona-intestinalis-modulates-responses-of-the-human-immune-system
#13
Angela Bonura, Aiti Vizzini, Sara Vlah, Francesco Gervasi, Alessandra Longo, Mario R Melis, Frank A Schildberg, Paolo Colombo
The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers' interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that are essential for shaping innate immune responses...
October 16, 2017: Immunobiology
https://www.readbyqxmd.com/read/29020495/effect-of-adalimumab-on-peripheral-blood-mononuclear-cells-in-non-infectious-uveitis
#14
Karoline Walscheid, Toni Weinhage, Dirk Foell, Carsten Heinz, Maren Kasper, Arnd Heiligenhaus
PURPOSE: This study analyzed the effect of adalimumab on peripheral blood mononuclear cells (PBMCs) in uveitis. METHODS: PBMCs and serum S100A12 levels from 14 uveitis patients and 28 healthy controls were analyzed. Patient samples were taken before (w0), and 6 (w6) and 12 (w12) weeks after initiation of adalimumab therapy. RESULTS: Monocytes expressing CD124, CD86, CD39, CD115, and MHCII were decreased in patients. Adalimumab induced CD86+ and CD39+ monocytes, and further decreased the frequency of MHCII- and CD124-positive cells...
October 11, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28980000/increased-indoleamine-2-3-dioxygenase-and-quinolinic-acid-expression-in-microglia-and-m%C3%A3-ller-cells-of-diabetic-human-and-rodent-retina
#15
Ping Hu, Nicholas H Hunt, Frank Arfuso, Lynn C Shaw, Mohammad Nasir Uddin, Meidong Zhu, Raj Devasahayam, Samuel J Adamson, Vicky L Benson, Tailoi Chan-Ling, Maria B Grant
Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels)...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28978031/hyperthermia-and-associated-changes-in-membrane-fluidity-potentiate-p2x7-activation-to-promote-tumor-cell-death
#16
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963731/ex-vivo-expanded-baboon-cd39%C3%A2-%C3%A2-regulatory-t-cells-prevent-rejection-of-porcine-islet-xenografts-in-nod-scid-il-2r%C3%AE-mice-reconstituted-with-baboon-peripheral-blood-mononuclear-cells
#17
Dandan Huang, Ya Wang, Wayne J Hawthorne, Min Hu, Joanne Hawkes, Heather Burns, Sussan Davies, Feng Gao, Yi Vee Chew, Shounan Yi, Philip J O'Connell
BACKGROUND: A high immunosuppressive burden is required for long-term islet xenograft survival in non-human primates even using genetically modified donor pigs. AIMS: We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. MATERIALS & METHODS: Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro...
September 30, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28959385/dominant-immunosuppression-of-dendritic-cell-function-by-prostate-cancer-derived-exosomes
#18
Josephine Salimu, Jason Webber, Mark Gurney, Saly Al-Taei, Aled Clayton, Zsuzsanna Tabi
Exosomes are a distinct population of extracellular vesicles of endocytic origin with a protein repertoire similar to the parent cell. Although tumour-derived exosomes harbour immunosuppressive characteristics, they also carry tumour antigens and thus potentially contribute to immune activation. The aim of this study was to examine the impact of prostate cancer exosomes on tumour antigen cross-presentation. DU145 cells, transduced with shRNA to knockdown Rab27a (DU145(KD)) that inhibits exosome secretion, triggered significantly stronger tumour-antigen-specific T cell responses when loaded onto dendritic cells (DC) than control DU145 cells...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28956227/various-n-glycoforms-differentially-upregulate-e-ntpdase-activity-of-the-ntpdase3-cd39l3-ecto-enzymatic-domain
#19
Alexander H Zhong, Z Gordon Jiang, Richard D Cummings, Simon C Robson
The GDA1/CD39 ecto-nucleoside triphosphate diphosphosphohydrolase (E-NTPDase) superfamily is a group of eight heavily glycosylated ecto-enzymes that hydrolyze extracellular nucleosides di- and tri-phosphates in the presence of divalent cations, to generate the monophosphate derivatives. This catalytic process differentially regulates a complex array of purinergic signaling responses. NTPDase3/CD39L3is dominantly expressed in pancreatic islet cells, where it may regulate insulin secretion, and has seven N-linked glycosylation sites with four close to five highly conserved domains called "apyrase conserved regions" (ACRs)...
September 27, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28955342/mass-cytometry-identifies-distinct-lung-cd4-t-cell-patterns-in-l%C3%A3-fgren-s-syndrome-and-non-l%C3%A3-fgren-s-syndrome-sarcoidosis
#20
Ylva Kaiser, Tadepally Lakshmikanth, Yang Chen, Jaromir Mikes, Anders Eklund, Petter Brodin, Adnane Achour, Johan Grunewald
Sarcoidosis is a granulomatous disorder of unknown etiology, characterized by accumulation of activated CD4(+) T cells in the lungs. Disease phenotypes Löfgren's syndrome (LS) and "non-LS" differ in terms of clinical manifestations, genetic background, HLA association, and prognosis, but the underlying inflammatory mechanisms largely remain unknown. Bronchoalveolar lavage fluid cells from four HLA-DRB1*03(+) LS and four HLA-DRB1*03(-) non-LS patients were analyzed by mass cytometry, using a panel of 33 unique markers...
2017: Frontiers in Immunology
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