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https://www.readbyqxmd.com/read/28644966/an-immunosuppressive-function-of-interleukin-35-in-chronic-hepatitis-c-virus-infection
#1
Siqi Liu, Qian Zhang, Xue Shao, Wenrui Wang, Chuanhui Zhang, Zhenjing Jin
Interleukin (IL)-35, a newly identified member of the IL-12 cytokine family, has been reported to suppress inflammation and induce immunotolerance. However, little is known regarding the role of IL-35 during chronic hepatitis C virus (HCV) infection. Herein, we measured the serum IL-35 concentration of 73 patients with hepatitis C and 22 healthy individuals, as well as further investigated the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) and on hepatocytes infected with HCV in cell culture (HCVcc)...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#2
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28644030/a-plc-%C3%AE-1-feedback-pathway-regulates-lck-substrate-phosphorylation-at-the-t-cell-receptor-and-slp-76-complex
#3
Judson Belmont, Tao Gu, Ashley Marie Mudd, Arthur R Salomon
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T cell receptor signaling events is incompletely understood. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck...
June 23, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28643902/modulation-of-antitumor-immunity-contributes-to-the-enhanced-therapeutic-efficacy-of-liposomal-oxaliplatin-in-mouse-model
#4
Taro Shimizu, Amr S Abu Lila, Miho Nishio, Yusuke Doi, Hidenori Ando, Masami Ukawa, Yu Ishima, Tatsuhiro Ishida
Immune modulation of the tumor microenvironment has been reported to participate to the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice via permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#5
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643491/association-of-foxp3-polymorphism-with-allograft-outcome-in-kidney-transplantation
#6
Hyewon Park, Nuri Lee, Ji Won In, Eun Youn Roh, Kyoung Un Park, Sue Shin, Jaeseok Yang, Eun Young Song
BACKGROUND: Forkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome. METHODS: Foxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital...
September 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28642882/tumor-related-exosomes-contribute-to-tumor-promoting-microenvironment-an-immunological-perspective
#7
REVIEW
Wuzhen Chen, Jingxin Jiang, Wenjie Xia, Jian Huang
Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28642803/transcriptomic-profiles-of-aging-in-na%C3%A3-ve-and-memory-cd4-cells-from-mice
#8
Jackson Taylor, Lindsay Reynolds, Li Hou, Kurt Lohman, Wei Cui, Stephen Kritchevsky, Charles McCall, Yongmei Liu
BACKGROUND: CD4+ T cells can be broadly divided into naïve and memory subsets, each of which are differentially impaired by the aging process. It is unclear if and how these differences are reflected at the transcriptomic level. We performed microarray profiling on RNA derived from naïve (CD44(low)) and memory (CD44(high)) CD4+ T cells derived from young (2-3 month) and old (28 month) mice, in order to better understand the mechanisms of age-related functional alterations in both subsets...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642760/interleukin-6-in-allogeneic-stem-cell-transplantation-its-possible-importance-for-immunoregulation-and-as-a-therapeutic-target
#9
REVIEW
Tor Henrik Anderson Tvedt, Elisabeth Ersvaer, Anders Aune Tveita, Øystein Bruserud
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28642347/counteracting-dysfunction-of-regulatory-t-cells-in-organ-transplantation
#10
Cees van Kooten
No abstract text is available yet for this article.
June 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28642280/granulocytes-as-modulators-of-dendritic-cell-function
#11
REVIEW
Annelot Breedveld, Tom Groot Kormelink, Marjolein van Egmond, Esther de Jong
Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4(+) T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (Tregs). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642148/biological-activity-of-glatiramer-acetate-on-treg-and-anti-inflammatory-monocytes-persists-for-more-than-10years-in-responder-multiple-sclerosis-patients
#12
Michela Spadaro, Francesca Montarolo, Simona Perga, Serena Martire, Federica Brescia, Simona Malucchi, Antonio Bertolotto
Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14(+)CD163(+) monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months...
June 19, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#13
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28641881/peripheral-blood-regulatory-t-cell-counts-as-a-predictive-biomarker-for-the-outcome-of-kidney-transplant-a-systematic-review
#14
Francisco Herrera-Gómez, Mónica Vásquez-Seoane, Waldo Del Aguila, Débora Martín-García, Álvaro Maurtua-Briseño Meiggs, Anunciación González-López, Beatriz Andrés-Martín, Álvaro Nava-Rebollo, Fernando Casquero-Fernández, Pilar Pascual-Núñez, Jesús Grande-Villoria, Jesús Bustamante-Bustamante, Carlos Ochoa-Sangrador, Claude Lambert, Alicia Mendiluce-Herrero
BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched...
June 19, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#15
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28639894/deregulated-expression-of-cdc6-as-bcr-abl-dependent-survival-factor-in-chronic-myeloid-leukemia-cells
#16
Jia-Hua Zhang, Yan-Li He, Rui Zhu, Wen Du, Jun-Hua Xiao
Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639574/mir-551b-5p-contributes-to-pathogenesis-of-vein-graft-failure-via-upregulating-early-growth-response-1-expression
#17
Ran Dong, Kui Zhang, Yue-Li Wang, Feng Zhang, Jian Cao, Ju-Bing Zheng, Hong-Jia Zhang
BACKGROUND: Vein graft failure (VGF) is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs (miRNAs) on the endothelial dysfunction involved in VGF. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray® V4 (PhalanxBio Inc...
July 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28638937/anti-gitr-antibody-treatment-increases-tcr-repertoire-diversity-of-regulatory-but-not-effector-t-cells-engaged-in-the-immune-response-against-b16-melanoma
#18
Bozena Scirka, Edyta Szurek, Maciej Pietrzak, Grzegorz Rempala, Pawel Kisielow, Leszek Ignatowicz, Arkadiusz Miazek
Crosslinking of glucocorticoid-induced TNF family-related receptor (GITR) with agonist antibodies restores cancer immunity by enhancing effector T cell (Teff) responses while interfering with intra-tumor regulatory T cell (Treg) stability and/or accumulation. However, how anti-GITR antibody infusion changes T cell receptor (TCR) repertoire of Teffs and Tregs engaged in anti-tumor immune response is unclear. Here, we used a transgenic mouse model (TCRmini) where T cells express naturally generated but limited TCR repertoire to trace the fate of individual T cells recognizing B16 melanoma in tumor-bearing mice, treated or non-treated with an anti-GITR monoclonal antibody DTA-1...
June 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28638851/mucosal-biopsy-shows-immunologic-changes-of-the-colon-in-patients-with-early-ms
#19
Adrian Mathias Moser, Walter Spindelboeck, Heimo Strohmaier, Christian Enzinger, Thomas Gattringer, Siegrid Fuchs, Franz Fazekas, Gregor Gorkiewicz, Philipp Wurm, Christoph Högenauer, Michael Khalil
OBJECTIVE: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS. METHODS: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28638744/azacytidine-prevents-experimental-xenogeneic-graft-versus-host-disease-without-abrogating-graft-versus-leukemia-effects
#20
Grégory Ehx, Gilles Fransolet, Laurence de Leval, Stéphanie D'Hondt, Sophie Lucas, Muriel Hannon, Loïc Delens, Sophie Dubois, Pierre Drion, Yves Beguin, Stéphanie Humblet-Baron, Frédéric Baron
The demethylating agent 5-azacytidine (AZA) has proven its efficacy in the treatment of myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-vs.-host disease (xGVHD) and graft-vs.-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo...
2017: Oncoimmunology
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