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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231392/from-dendritic-cells-to-b-cells-dysfunctions-during-hiv-1-infection-tfh-at-the-cross-road
#2
REVIEW
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#3
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28231043/transient-oxytocin-signaling-primes-the-development-and-function-of-excitatory-hippocampal-neurons
#4
Silvia Ripamonti, Mateusz C Ambrozkiewicz, Francesca Guzzi, Marta Gravati, Gerardo Biella, Ingo Bormuth, Matthieu Hammer, Liam P Tuffy, Albrecht Sigler, Hiroshi Kawabe, Katsuhiko Nishimori, Mauro Toselli, Nils Brose, Marco Parenti, JeongSeop Rhee
Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons...
February 23, 2017: ELife
https://www.readbyqxmd.com/read/28230865/erbb4-signaling-stimulates-pro-inflammatory-macrophage-apoptosis-and-limits-colonic-inflammation
#5
Michael A Schumacher, Matija Hedl, Clara Abraham, Jessica K Bernard, Patricia R Lozano, Jonathan J Hsieh, Dana Almohazey, Edie B Bucar, Shivesh Punit, Peter J Dempsey, Mark R Frey
Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230645/clinical-scale-rapid-autologous-bk-virus-specific-t-cell-line-generation-from-kidney-transplant-recipients-with-active-viremia-for-adoptive-immunotherapy
#6
Caroline Lamarche, Julie Orio, Victoria Georges-Tobar, Thomas Pincez, Mathieu Goupil, Amina Dahmani, Cedric Carli C, Ann Brasey, Lambert Busque, Jean-Sébastien Delisle
BACKGROUND: Polyomavirus-associated nephropathy (PVAN) following BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulation/expansion offers the possibility to generate BK-specific T cell lines for adoptive immunotherapy. The objective of this study was to develop and characterize a clinical scale protocol to generate BK-specific T cell lines from viremic KTR...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230210/synergistic-suppression-of-autoimmune-arthritis-through-concurrent-treatment-with-tolerogenic-dc-and-msc
#7
Rong Li, Yujuan Zhang, Xiufen Zheng, Shanshan Peng, Keng Yuan, Xusheng Zhang, Weiping Min
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229976/immune-modulation-by-dendritic-cell-based-cancer-vaccines
#8
Chaitanya Kumar, Sakshi Kohli, Poonamalle Parthasarathy Bapsy, Ashok Kumar Vaid, Minish Jain, Venkata Sathya Suresh Attili, Bandana Sharan
The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour microenvironment or by revitalizing the immune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review, current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines are discussed...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229819/dabigatran-aggravates-topoisomerase-i-peptide-loaded-dendritic-cells-induced-lung-and-skin-fibrosis
#9
Heena Mehta, Philippe-Olivier Goulet, Jade Desjardins, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
OBJECTIVES: Dysregulated coagulation cascade has been implicated in development of fibrosis in systemic sclerosis (SSc). Thrombin, a key mediator of the coagulation pathway, has both proinflammatory and procoagulant properties. Here, we evaluated the efficacy of oral dabigatran, a direct thrombin inhibitor, on topoisomerase I dendritic cells (TOPOIA DCs)-induced lung and skin fibrosis, an experimental model of SSc. METHODS: Mice were repeatedly immunized with TOPOIA DCs...
February 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28229507/a-samhd1-mutation-associated-with-aicardi-gouti%C3%A3-res-syndrome-uncouples-the-ability-of-samhd1-to-restrict-hiv-1-from-its-ability-to-downmodulate-type-i-interferon-in-humans
#10
Tommy E White, Alberto Brandariz-Nuñez, Alicia Martinez-Lopez, Caitlin Knowlton, Gina Lenzi, Baek Kim, Dmitri Ivanov, Felipe Diaz-Griffero
Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28229217/foxo3-estrogen-receptor-alpha-and-androgen-receptor-impact-tumor-growth-rate-and-infiltration-of-dendritic-cell-subsets-differentially-between-male-and-female-mice
#11
Matthew G Thompson, Daniel S Peiffer, Michelle Larson, Flor Navarro, Stephanie K Watkins
Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system...
February 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28229087/modeling-williams-syndrome-with-induced-pluripotent-stem-cells
#12
Thanathom Chailangkarn, Alysson R Muotri
The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#13
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228755/dysregulation-of-socs-mediated-negative-feedback-of-cytokine-signaling-in-carcinogenesis-and-its-significance-in-cancer-treatment
#14
REVIEW
Mengmeng Jiang, Wen-Wen Zhang, Pengpeng Liu, Wenwen Yu, Ting Liu, Jinpu Yu
Suppressor of cytokine signaling (SOCS) proteins are major negative feedback regulators of cytokine signaling mediated by the Janus kinase (JAK)-signal transducer and activator of transcription signaling pathway. In particular, SOCS1 and SOCS3 are strong inhibitors of JAKs and can play pivotal roles in the development and progression of cancers. The abnormal expression of SOCS1 and SOCS3 in cancer cells is associated with the dysregulation of cell growth, migration, and death induced by multiple cytokines and hormones in human carcinomas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228590/a-polymorphism-within-the-internal-fusion-loop-of-the-ebola-virus-glycoprotein-modulates-host-cell-entry
#15
Markus Hoffmann, Lisa Crone, Erik Dietzel, Jennifer Paijo, Mariana González-Hernández, Inga Nehlmeier, Ulrich Kalinke, Stephan Becker, Stefan Pöhlmann
The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two non-human primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228559/targeting-influenza-virus-hemagglutinin-to-xcr1-dendritic-cells-in-the-absence-of-receptor-mediated-endocytosis-enhances-protective-antibody-responses
#16
Arnar Gudjonsson, Anna Lysén, Sreekumar Balan, Vibeke Sundvold-Gjerstad, Catharina Arnold-Schrauf, Lisa Richter, Espen S Bækkevold, Marc Dalod, Bjarne Bogen, Even Fossum
Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge...
February 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28228546/a-minimal-actomyosin-based-model-predicts-the-dynamics-of-filopodia-on-neuronal-dendrites
#17
Olena O Marchenko, Sulagna Das, Ji Yu, Igor L Novak, Vladimir I Rodionov, Nadia Efimova, Tatyana Svitkina, Charles W Wolgemuth, Leslie M Loew
Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various filopodial behaviors...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#18
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228271/antigen-primed-cd8-t-cells-call-dcs-for-back-up
#19
Marianne Burbage, Sebastian Amigorena
Encounters between naive T lymphocytes and dendritic cells (DCs) bearing adequate co-stimulatory signals are rare. In this issue of Immunity, Brewitz et al. (2017) show that chemokines secreted by CD8(+) T cells recruit myeloid and plasmacytoid DCs that in turn boost CD8(+) T cell activation.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#20
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
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