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https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#1
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098832/therapeutic-potential-of-targeting-the-th17-treg-axis-in-autoimmune-disorders
#2
REVIEW
Patrizia Fasching, Martin Stradner, Winfried Graninger, Christian Dejaco, Johannes Fessler
A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the  pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098283/high-precision-localized-proton-gradients-and-fluxes-generated-by-a-microelectrode-device-induce-differential-growth-behaviors-of-pollen-tubes
#3
Chengzhi Hu, Hannes Vogler, Marianne Aellen, Naveen Shamsudhin, Bumjin Jang, Jan T Burri, Nino Läubli, Ueli Grossniklaus, Salvador Pané, Bradley J Nelson
Pollen tubes are tip-growing plant cells that deliver the sperm cells to the ovules for double fertilization of the egg cell and the endosperm. Various directional cues can trigger the reorientation of pollen tube growth direction on their passage through the female tissues. Among the external stimuli, protons serve an important, regulatory role in the control of pollen tube growth. The generation of local guidance cues has been challenging when investigating the mechanisms of perception and processing of such directional triggers in pollen tubes...
January 18, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#4
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#5
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28096525/toll-like-receptor-4-signaling-in-high-mobility-group-box-1-protein-1-mediated-the-suppression-of-regulatory-t-cells
#6
Chunyan Luo, Huiting Liu, Hu Wang, Jiajun Wang
BACKGROUND Treg cells play a central role in the suppression of immune response, and their suppressive capacity can be modulated by toll-like receptor (TLR) ligands. However, the detailed pathway of TLR ligand modulation is still unknown. The present study aimed to evaluate the effect of the high mobility group box-1 protein 1 (HMGB1) and lipopolysaccharide (LPS) on Treg cells through TLR4 signaling. MATERIAL AND METHODS Treg cells were purified from healthy human peripheral blood mononuclear cells (PBMCs) by magnetic-bead activity cell sorting (MACS), blocked by anti-TLR4 monoclonal antibody, and then incubated with different concentration of LPS or HMGB1...
January 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28096513/targeting-tnfr2-with-antagonistic-antibodies-inhibits-proliferation-of-ovarian-cancer-cells-and-tumor-associated-tregs
#7
Heather Torrey, John Butterworth, Toshiyuki Mera, Yoshiaki Okubo, Limei Wang, Danielle Baum, Audrey Defusco, Sara Plager, Sarah Warden, Daniel Huang, Eva Vanamee, Rosemary Foster, Denise L Faustman
Major barriers to cancer therapy include the lack of selective inhibitors of regulatory T cells (Tregs) and the lack of broadly applicable ways to directly target tumors through frequently expressed surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is an attractive target protein because of its restricted abundance to highly immunosuppressive Tregs and oncogenic presence on human tumors. We characterized the effect of TNFR2 inhibition using antagonistic antibodies. In culture-based assays, we found that two TNFR2 antagonists inhibited Treg proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096507/de-novo-phosphorylation-and-conformational-opening-of-the-tyrosine-kinase-lck-act-in-concert-to-initiate-t-cell-receptor-signaling
#8
Lars Philipsen, Amarendra V Reddycherla, Roland Hartig, Janine Gumz, Matthias Kästle, Andreas Kritikos, Mateusz P Poltorak, Yury Prokazov, Evgeny Turbin, André Weber, Werner Zuschratter, Burkhart Schraven, Luca Simeoni, Andreas J Müller
The enzymatic activity of the Src family tyrosine kinase p56(Lck) (Lck) is tightly controlled by differential phosphorylation of two tyrosine residues, Tyr(394) and Tyr(505) Phosphorylation of Tyr(394) and the conformational opening of Lck are believed to activate the kinase, whereas Tyr(505) phosphorylation is thought to generate a closed, inactive conformation of Lck. We investigated whether the conformation of Lck and its phosphorylation state act in concert to regulate the initiation of T cell receptor (TCR) signaling...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096506/targeting-tnfr2-an-immune-checkpoint-stimulator-and-oncoprotein-is-a-promising-treatment-for-cancer
#9
REVIEW
Xin Chen, Joost J Oppenheim
Tumor necrosis factor receptor 2 (TNFR2) is expressed both by some cancer cells and by tumor-infiltrating immunosuppressive CD4(+)FoxP3(+) regulatory T cells (Tregs). TNFR2 stimulates the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses, and promotes cancer cell survival and tumor growth. In this issue of Science Signaling, Torrey et al found that dominant antagonistic antibodies against human TNFR2 may be a potential therapy for ovarian cancer patients by simultaneously suppressing Treg activity and inducing the death of the cancer cells...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#10
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096298/mfg-e8-derived-peptide-attenuates-adhesion-and-migration-of-immune-cells-to-endothelial-cells
#11
Yohei Hirano, Weng-Lang Yang, Monowar Aziz, Fangming Zhang, Barbara Sherry, Ping Wang
Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) plays an immunomodulatory role in inflammatory diseases. MFG-E8-derived short peptide (MSP68) greatly reduces neutrophil infiltration and injury in the lung during sepsis. In this study, we examined the effect of MSP68 on chemotaxis of various immune cells and its regulatory mechanism. Bone marrow-derived neutrophils (BMDNs) from C57BL/6 mice, human monocyte THP-1 cell line, and human T lymphocyte Jurkat cell line were used for adhesion and migration assays using a Transwell method in the presence of MSP68...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28095355/immune-regulatory-network-in-successful-pregnancy-and-reproductive-failures
#12
REVIEW
Mahnaz Ghaebi, Mohammad Nouri, Aliyeh Ghasemzadeh, Laya Farzadi, Farhad Jadidi-Niaragh, Majid Ahmadi, Mehdi Yousefi
Maternal immune system must tolerate semiallogenic fetus to establish and maintain a successful pregnancy. Despite the existence of several strategies of trophoblast to avoid recognition by maternal leukocytes, maternal immune system may react against paternal alloantigenes. Leukocytes are important components in decidua. Not only T helper (Th)1/Th2 balance, but also regulatory T (Treg) cells play an important role in pregnancy. Although the frequency of Tregs is elevated during normal pregnancies, their frequency and function are reduced in reproductive defects such as recurrent miscarriage and preeclampsia...
January 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28095351/level-of-granzyme-b-positive-t-regulatory-cells-is-a-strong-predictor-biomarker-of-acute-graft-versus-host-disease-after-day-30-after-allo-hsct
#13
Mikhail Y Drokov, Julia O Davydova, Larisa A Kuzmina, Irina V Galtseva, Nikolay M Kapranov, Vera A Vasilyeva, Darya S Dubnyak, Olga M Koroleva, Ekaterina D Mikhalcova, Natalia N Popova, Elena N Parovichnikova, Valery G Savchenko
Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells...
January 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28095207/the-constitutive-endopolygalacturonase-tvpg2-regulates-the-induction-of-plant-systemic-resistance-by-trichoderma-virens
#14
Sabrina Sarrocco, Fabiola Matarese, Riccardo Baroncelli, Giovanni Vannacci, Verena Seidl-Seiboth, Christian Peter Kubicek, Mariarosaria Vergara
Trichoderma spp. are opportunistic fungi some of which are commonly present in the rhizosphere. Several species, such as Trichoderma virens, are also efficient biocontrol agents against phytopathogenic fungi and exert beneficial effects on plants. These effects are the consequence of interactions between Trichoderma and plant roots, which trigger enhanced plant growth and induce plant resistance. We have previously shown that T. virens I10 expresses two endopolygalacturonase genes, tvpg1 and tvpg2, during the interaction with plant roots; tvpg1 is inducible while tvpg2 is constitutively transcribed...
January 17, 2017: Phytopathology
https://www.readbyqxmd.com/read/28094847/increased-regulatory-t-cell-graft-content-is-associated-with-improved-outcome-in-haematopoietic-stem-cell-transplantation-a-systematic-review
#15
Sheila A Fisher, Abigail Lamikanra, Carolyn Dorée, Betty Gration, Pat Tsang, Robert D Danby, David J Roberts
Allogeneic haematopoietic stem cell transplant (HSCT) recipients are at increased risk of morbidity and mortality, often due to the development of acute or chronic graft-versus-host disease (GVHD). Low numbers or proportions of regulatory T cells (Tregs) have been reported in patients who develop GVHD. We undertook a systematic review of studies that reported the Treg composition of HSCT grafts in patients with haematological malignancies. Fourteen eligible studies were identified, eight of which stratified patients by Tregs (absolute dose or ratio to CD3+ or CD4+ cells)...
January 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28094754/comparable-therapeutic-potential-of-umbilical-cord-mesenchymal-stem-cells-in-collagen-induced-arthritis-to-tnf-inhibitor-or-anti-cd20-treatment
#16
Yue Sun, Wei Kong, Saisai Huang, Bingyu Shi, Hanyu Zhang, Weiwei Chen, Huayong Zhang, Cheng Zhao, Xiaojun Tang, Genhong Yao, Xuebing Feng, Lingyun Sun
OBJECTIVES: The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies. METHODS: CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring...
January 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28094574/inferring-a-role-for-methylation-of-intergenic-dna-in-the-regulation-of-genes-aberrantly-expressed-in-precursor-b-cell-acute-lymphoblastic-leukemia
#17
Md Almamun, Olha Kholod, Alexei J Stuckel, Benjamin T Levinson, Nathan T Johnson, Gerald L Arthur, J Wade Davis, Kristen H Taylor
A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors (TF) known to play roles in differentiation and B-cell development in a lymphoblastoid cell line...
January 17, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28094101/retinoic-acid-and-immune-homeostasis-a-balancing-act
#18
REVIEW
Martje N Erkelens, Reina E Mebius
In the immune system, the vitamin A metabolite retinoic acid (RA) is known for its role in inducing gut-homing molecules in T and B cells, inducing regulatory T cells (Tregs), and promoting tolerance. However, it was suggested that RA can have a broad spectrum of effector functions depending on the local microenvironment. Under specific conditions, RA can also promote an inflammatory environment. We discuss the dual role of RA in immune responses and how this might be regulated. Furthermore, we focus on the role of RA in autoimmune diseases and whether RA might be used as a therapeutic agent...
January 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-faslpr-mice
#19
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093521/oncostatin-m-suppresses-activation-of-il-17-th17-via-socs3-regulation-in-cd4-t-cells
#20
Hye-Jin Son, Seung Hoon Lee, Seon-Yeong Lee, Eun-Kyung Kim, Eun-Ji Yang, Jae-Kyung Kim, Hyeon-Beom Seo, Sung-Hwan Park, Mi-La Cho
Oncostatin M (OSM) is a pleiotropic cytokine and a member of the IL-6 family. It has both proinflammatory and anti-inflammatory functions and is involved in the activation of STAT3 and STAT5. Rheumatoid arthritis is an autoimmune disease that causes chronic and excessive inflammation. Rheumatoid arthritis can lead to induction of Th17 cells, which express IL-17. The aim of this study was to measure the effects of OSM on the proliferation of regulatory T cells and Th17 cells from mice. IL-2 immune complex suppressed the development of collagen-induced arthritis in mice and altered the regulatory T/Th17 cell balance by increasing OSM expression...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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