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https://www.readbyqxmd.com/read/28109145/-short-term-use-of-rapamycin-combined-with-tregs-prolongs-mouse-cardiac-graft-survival-but-attenuates-recipient-s-anti-tumor-immunity
#1
Ting Yan, Chen Luo, Xianmo Yang, Lei Ji, Shiqiao Luo
Objective To study the effect of short-term use of rapamycin(Rap) combined with regulatory T cells (Tregs) on the long-time survival of allogeneic mouse cardiac transplant, and its impact on the anti-tumor immunity of recipient. MethodsMouse Tregs were purified from recipients' spleen by magnetic activated cell sorting (MACS), and expanded by CD3/CD28 monoclonal antibody immunomagnetic beads and 2000 U/mL recombinant mouse IL-2 (rmIL-2) ex vivo. The purity was tested by fluorescence-activated cell sorting (FACS)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109143/-decreased-number-and-immune-activity-of-splenic-t-lymphocytes-in-mice-exposed-to-hypoxia-at-high-altitude
#2
Xiaona Zhang, Jidong Li, Fangjie Hu, Shilan Gao, Xiaoyan Pu, Sheng Yong
Objective To explore the changes of splenic T lymphocyte subsets and functions in mice under high-altitude hypoxic conditions. Methods After mice were exposed to an altitude of 400 m, 2200 m and 4200 m for 30 days, ELISA was used to detect the concentrations of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in the cultured splenocyte supernatant; MTT assay was used to analyze the proliferation of splenic T lymphocytes; flow cytometry was performed to examine the alterations of splenic T lymphocyte subsets...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109047/novel-antiplatelet-role-for-a-protein-disulfide-isomerase-targeted-peptide-evidence-of-covalent-binding-to-c-terminal-cghc-redox-motif
#3
H R Sousa, R S Gaspar, E M L Sena, S A da Silva, J L de L Fontelles, T L S Araújo, M Mastrogiovanni, D M Fries, A P S Azevedo-Santos, F R M Laurindo, A Trostchansky, A M Paes
Protein disulfide isomerase (PDI) plays a major role in platelet aggregation and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized this peptide would also inhibit platelet aggregation by association to surface PDI. Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109042/expression-and-characterization-of-a-codon-optimized-blood-coagulation-factor-viii
#4
S A Shestopal, J-J Hao, E Karnaukhova, Y Liang, M V Ovanesov, M Lin, J H Kurasawa, T K Lee, J H McVey, A G Sarafanov
BACKGROUND: Production of recombinant factor VIII (FVIII) is challenging due to its low expression. It was previously shown that codon-optimization of a B domain-deleted FVIII (BDD-FVIII) cDNA resulted in increased protein expression. However, it is well-recognized that synonymous mutations may affect the protein structure and function. OBJECTIVES: To compare biochemical properties of a BDD-FVIII expressed from codon-optimized (CO) and the wild-type (WT) cDNAs. METHODS: Each variant of the BDD-FVIII was expressed in several independent CHO cell lines, generated using a lentiviral platform...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#5
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108989/tigit-signaling-pathway-negatively-regulates-cd4-t-cell-responses-in-systemic-lupus-erythematosus
#6
Lie Mao, Hongyan Hou, Shiji Wu, Yu Zhou, Juan Wang, Jing Yu, Xiaohui Wu, Yanfang Lu, Liyan Mao, Munyemana Jean Bosco, Feng Wang, Ziyong Sun
B lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T cell-dependent, and CD4(+) T cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4(+) T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4(+) T cells. Here, we addressed the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4(+) T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108987/activation-of-sirt1-by-human-chorionic-gonadotropin-exerts-a-therapeutic-effect-on-hepatic-injury-and-inflammation
#7
Caroline Steinmetz, Anubha Kashyap, Nataliya Zhivkova, Henry Alizor, Isabell Ernst, Daniela Gottfried-Brand, Henning Janssen, Andreas Teufel, Henning Schulze-Bergkamen, Johannes Lotz, Jürgen Kuball, Matthias Theobald, Michael Heise, Hauke Lang, Peter R Galle, Dennis Strand, Susanne Strand
: The incidence and prevalence of inflammatory liver diseases has increased over the last years but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune suppressive mechanisms of the human pregnancy hormone chorionic gonadotropin (hCG) in the liver. HCG signaling activates SIRT1, which deacetylates FOXO3a, leading to repression of pro-apoptotic gene expression...
January 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28108950/t-cell-receptor-engineered-t-cells-for-cancer-treatment-current-status-and-future-directions
#8
REVIEW
Yu Ping, Chaojun Liu, Yi Zhang
T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1)...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108937/glycyrrhizin-ameliorates-experimental-colitis-through-attenuating-interleukin-17-producing-t-cell-responses-via-regulating-antigen-presenting-cells
#9
Xiangyu Chen, Dai Fang, Lingyun Li, Liyong Chen, Qirui Li, Feili Gong, Min Fang
Glycyrrhizin, a component of Chinese medicine licorice root, has the ability to inhibit the functions of high-mobility group box 1 (HMGB1). While glycyrrhizin is known to have anti-inflammatory activities, the underlying mechanisms by which glycyrrhizin inhibits inflammation during the development of trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis are not well understood. This study systemically examined the regulatory effects of glycyrrhizin on inflammatory response in TNBS-induced murine colitis and explored the potential mechanisms involved in this process...
January 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#10
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T helper (Th1) cells and CD8(+) T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity towards CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108622/a-genome-wide-loss-of-function-screen-identifies-slc26a2-as-a-novel-mediator-of-trail-resistance
#11
Lina Dimberg, Christina G Towers, Kian Behbakht, Taylor Hotz, Jihye Kim, Susan P Fosmire, Christopher C Porter, Aik-Choon Tan, Andrew Thorburn, Heide L Ford
: TNF-related apoptosis inducing ligand (TRAIL) is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108610/circulating-cxcr5-pd-1-icos-follicular-t-helper-cells-are-increased-close-to-the-diagnosis-of-type-1-diabetes-in-children-with-multiple-autoantibodies
#12
Tyyne Viisanen, Emmi-Leena Ihantola, Kirsti Näntö-Salonen, Heikki Hyöty, Noora Nurminen, Jenni Selvenius, Auni Juutilainen, Leena Moilanen, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Although type 1 diabetes (T1D) is primarily perceived as a T cell-driven autoimmune disease, islet autoantibodies are the best currently available biomarker for autoimmunity and disease risk. These antibodies are produced by autoreactive B cells, the activation of which is largely dependent on the function of CD4(+)CXCR5(+) follicular T helper cells (Tfh). In this study, we have comprehensively characterized the Tfh- as well as B-cell compartments in a large cohort of children with newly diagnosed T1D or at different stages of preclinical T1D...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108608/macrophage-proliferation-sustains-adipose-tissue-inflammation-in-formerly-obese-mice
#13
Brian F Zamarron, Taleen A Mergian, Kae Won Cho, Gabriel Martinez-Santibanez, Danny Luan, Kanakadurga Singer, Jennifer L DelProposto, Lynn M Geletka, Lindsey A Muir, Carey N Lumeng
Obesity causes dramatic proinflammatory changes in the adipose tissue immune environment, but relatively little is known regarding how this inflammation responds to weight loss (WL). To understand the mechanisms by which meta-inflammation resolves during WL, we examined adipose tissue leukocytes in mice after withdrawal of a high-fat diet. After 8 weeks of WL, mice achieved similar weights and glucose tolerance values as age-matched lean controls but showed abnormal insulin tolerance. Despite fat mass normalization, total and CD11c(+) adipose tissue macrophage (ATM) content remained elevated in WL mice for up to 6 months and was associated with persistent fibrosis in adipose tissue...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108597/bispecific-antibodies-and-antibody-drug-conjugates-adcs-bridging-her2-and-prolactin-receptor-improve-efficacy-of-her2-adcs
#14
Julian Andreev, Nithya Thambi, Andres E Perez Bay, Frank J Delfino, Joel H Martin, Marcus P Kelly, Jessica R Kirshner, Ashique Rafique, Arthur Kunz, Thomas Nittoli, Douglas MacDonald, Christopher Daly, William Olson, Gavin Thurston
The properties of cell surface proteins targeted by Antibody-drug conjugates (ADCs) have not been fully exploited; of particular importance are the rate of internalization and the route of intracellular trafficking. In this study we compared the trafficking of HER2, which is the target of the clinically approved ADC ado-trastuzumab emtansine (T-DM1), with that of prolactin receptor (PRLR), another potential target in breast cancer. In contrast to HER2, we found that PRLR is rapidly and constitutively internalized, and traffics efficiently to lysosomes, where it is degraded...
January 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28108557/low-level-mhc-class-ii-expression-leads-to-suboptimal-th-cell-response-increased-autoaggression-and-heightened-cytokine-inducibility
#15
Yi-Ting Chen, Yu-Chia Su, Mei-Ling Chang, Pi-Fang Tsai, John T Kung
The development and activation of MHC class II (MHC-II)-restricted CD4(+) T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A(12%), with ∼8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A(100%) and I-A(12%) mice are highly similar with respect to the numbers of double-positive thymocytes, CD4(+)CD8(-) T cells, regulatory T cells, CD4(+) T cell marker expression, lifespan, and Th/regulatory T cell function...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#16
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108486/regulation-of-the-immune-response-by-tgf-%C3%AE-from-conception-to-autoimmunity-and-infection
#17
Shomyseh Sanjabi, Soyoung A Oh, Ming O Li
Transforming growth factor β (TGF-β) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-β alters immunity under various conditions. Under steady-state conditions, TGF-β regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-β inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral (p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges...
January 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28108463/targeting-glioblastoma-with-car-t-cells
#18
(no author information available yet)
CAR T cells targeting IL13Rα2 proved effective against recurrent multifocal leptomeningeal glioblastoma, according to a case report. Direct delivery of the therapy into the cerebrospinal fluid was well tolerated, completely eliminating the patient's brain and spinal tumors for 7.5 months, during which the patient resumed his normal activities.
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28108449/quantification-of-fibrous-spatial-point-patterns-from-single-molecule-localization-microscopy-smlm-data
#19
Ruby Peters, Marta Benthem Muñiz, Juliette Griffié, David J Williamson, George W Ashdown, Christian D Lorenz, Dylan M Owen
MOTIVATION: Unlike conventional microscopy which produces pixelated images, SMLM produces data in the form of a list of localization coordinates - a spatial point pattern (SPP). Often, such SPPs are analyzed using cluster analysis algorithms to quantify molecular clustering within, for example, the plasma membrane. While SMLM cluster analysis is now well developed, techniques for analyzing fibrous structures remain poorly explored. RESULTS: Here, we demonstrate statistical methodology, based on Ripley's K-function to quantitatively assess fibrous structures in 2D SMLM data sets...
January 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#20
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
January 17, 2017: Biochimica et Biophysica Acta
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