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https://www.readbyqxmd.com/read/28640917/human-hantavirus-infection-elicits-pronounced-redistribution-of-mononuclear-phagocytes-in-peripheral-blood-and-airways
#1
Saskia Scholz, Faezzah Baharom, Gregory Rankin, Kimia T Maleki, Shawon Gupta, Sindhu Vangeti, Jamshid Pourazar, Andrea Discacciati, Jonas Höijer, Matteo Bottai, Niklas K Björkström, Johan Rasmuson, Magnus Evander, Anders Blomberg, Hans-Gustaf Ljunggren, Jonas Klingström, Clas Ahlm, Anna Smed-Sörensen
Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis...
June 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#2
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#3
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28636433/immunogenicity-of-ags-004-dendritic-cell-therapy-in-patients-treated-during-acute-hiv-infection
#4
Cynthia L Gay, Mark A DeBenedette, Irina Y Tcherepanova, Alicia Gamble, Whitney E Lewis, Anna B Cope, JoAnn D Kuruc, Kara S McGee, Mary F Kearney, John M Coffin, Nancie M Archin, Charles B Hicks, Joseph J Eron, Charles A Nicolette, David M Margolis
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4(+) T-cell infection (RCI) was measured by quantitative viral outgrowth assay...
June 21, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28623238/a-normal-genetic-variation-modulates-synaptic-mmp-9-protein-levels-and-the-severity-of-schizophrenia-symptoms
#5
Katarzyna Lepeta, Katarzyna J Purzycka, Katarzyna Pachulska-Wieczorek, Marina Mitjans, Martin Begemann, Behnam Vafadari, Krystian Bijata, Ryszard W Adamiak, Hannelore Ehrenreich, Magdalena Dziembowska, Leszek Kaczmarek
Matrix metalloproteinase 9 (MMP-9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype-based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP-9 rs20544 C/T single-nucleotide polymorphism (SNP) located in the 3'untranslated region (UTR) and the severity of a chronic delusional syndrome...
June 16, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28620074/regulatory-bc1-rna-in-cognitive-control
#6
Anna Iacoangeli, Aderemi Dosunmu, Taesun Eom, Dimitre G Stefanov, Henri Tiedge
Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and excessive cortical oscillations in the γ frequency band. Here we asked whether BC1 RNA control is also required for higher brain functions such as learning, memory, or cognition...
July 2017: Learning & Memory
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#7
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28608855/mice-lacking-the-chromodomain-helicase-dna-binding-5-chromatin-remodeler-display-autism-like-characteristics
#8
M T Pisansky, A E Young, M B O'Connor, I I Gottesman, A Bagchi, J C Gewirtz
Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs...
June 13, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28586072/treatment-of-colon-cancer-cells-with-5-fluorouracil-can-improve-the-effectiveness-of-rna-transfected-antitumor-dendritic-cell-vaccine
#9
Carolina V De Almeida, Jofer A Zamame, Graziela G Romagnoli, Cecilia P Rodrigues, Marianna B Magalhães, Amedeo Amedei, Ramon Kaneno
Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT‑116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT‑116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells...
June 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28584989/beta-glucan-particles-as-vaccine-adjuvant-carriers
#10
Zeynep Mirza, Ernesto R Soto, Fusun Dikengil, Stuart M Levitz, Gary R Ostroff
Glucan particles (GPs) are spherical hollow particles derived from Saccharomyces cerevisiae cell walls and mainly consist of β-1, 3-D-glucans. The inner hollow cavity of glucan particles can be loaded with different compounds, including protein antigens, and delivered to macrophages and dendritic cells. Moreover, the GP delivery system possesses β-glucan's intrinsic immunostimulatory properties. Therefore, GPs serve as both an antigen-presenting cell-targeted delivery system and an adjuvant.Here, we describe the production of GPs from S...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28584128/bcl11b-and-combinatorial-resolution-of-cell-fate-in-the-t-cell-gene-regulatory-network
#11
William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg
T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28578354/concurrent-ccr7-overexpression-and-relb-knockdown-in-immature-dendritic-cells-induces-immune-tolerance-and-improves-skin-graft-survival-in-a-murine-model
#12
Zhiwei Dong, Yajie Chen, Yuan Peng, Fan Wang, Zichen Yang, Guangtao Huang, Yu Chen, Zhiqiang Yuan, Tongtong Cao, Yizhi Peng
BACKGROUND/AIMS: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. METHODS & RESULTS: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression...
June 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28572564/plasmacytoid-dendritic-cells-appear-inactive-during-sub-microscopic-plasmodium-falciparum-blood-stage-infection-yet-retain-their-ability-to-respond-to-tlr-stimulation
#13
Jessica R Loughland, Gabriela Minigo, Derek S Sarovich, Matt Field, Peta E Tipping, Marcela Montes de Oca, Kim A Piera, Fiona H Amante, Bridget E Barber, Matthew J Grigg, Timothy William, Michael F Good, Denise L Doolan, Christian R Engwerda, Nicholas M Anstey, James S McCarthy, Tonia Woodberry
Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28566250/local-somatodendritic-translation-and-hyperphosphorylation-of-tau-protein-triggered-by-ampa-and-nmda-receptor-stimulation
#14
Shunsuke Kobayashi, Toru Tanaka, Yoshiyuki Soeda, Osborne F X Almeida, Akihiko Takashima
Tau is a major component of the neurofibrillary tangles (NFT) that represent a pathological hallmark of Alzheimer's disease (AD). Although generally considered an axonal protein, Tau is found in the somato-dendritic compartment of degenerating neurons and this redistribution is thought to be a trigger of neurodegeneration in AD. Here, we show the presence of tau mRNA in a dendritic ribonucleoprotein (RNP) complex that includes Ca2(+)-calmodulin dependent protein kinase (CaMK)IIα mRNA and that is translated locally in response to glutamate stimulation...
May 17, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28564605/a-tlr3-specific-adjuvant-relieves-innate-resistance-to-pd-l1-blockade-without-cytokine-toxicity-in-tumor-vaccine-immunotherapy
#15
Yohei Takeda, Keisuke Kataoka, Junya Yamagishi, Seishi Ogawa, Tsukasa Seya, Misako Matsumoto
Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28556833/blockade-of-interleukin-6-receptor-in-the-periphery-promotes-rapid-and-sustained-antidepressant-actions-a-possible-role-of-gut-microbiota-brain-axis
#16
J-C Zhang, W Yao, C Dong, C Yang, Q Ren, M Ma, K Hashimoto
Depression is a common, severe and chronic psychiatric disease. Although the currently available antidepressants have been used in the treatment of depression, their beneficial effects are limited. Accumulating evidence suggests that pro-inflammatory cytokines such as interleukin-6 (IL-6) have an important role in the pathogenesis of depression. This study was undertaken to examine whether anti-mouse IL-6 receptor antibody (MR16-1) induces antidepressant effects in a social defeat stress model. Intravenous injection of MR16-1 induced rapid-onset and long-lasting antidepressant effects in susceptible mice after social defeat stress through its anti-inflammatory actions...
May 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28555535/family-environments-and-leukocyte-transcriptome-indicators-of-a-proinflammatory-phenotype-in-children-and-parents
#17
Theodore F Robles, Rena L Repetti, Bridget M Reynolds, Paul J Chung, Jesusa M G Arevalo, Steven W Cole
High conflict and low warmth in families may contribute to immune cells developing a tendency to respond to threats with exaggerated inflammation that is insensitive to inhibitory signaling. We tested associations between family environments and expression of genes bearing response elements for transcription factors that regulate inflammation: nuclear factor kappa B (NF-κB) and glucocorticoid receptor. The overall sample (47 families) completed interviews, questionnaires, and 8-week daily diary assessments of conflict and warmth, which were used to create composite family conflict and warmth scores...
May 30, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28555386/molecular-pathogenesis-of-viral-hemorrhagic-fever
#18
REVIEW
Christopher F Basler
The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation...
May 29, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28543982/the-rna-binding-protein-caper-is-required-for-sensory-neuron-development-in-drosophila-melanogaster
#19
Eugenia C Olesnicky, Jeremy M Bono, Laura Bell, Logan T Schachtner, Meghan C Lybecker
BACKGROUND: Alternative splicing mediated by RNA-binding proteins (RBPs) is emerging as a fundamental mechanism for the regulation of gene expression. Alternative splicing has been shown to be a widespread phenomenon that facilitates the diversification of gene products in a tissue specific manner. Although defects in alternative splicing are rooted in many neurological disorders, only a small fraction of splicing factors have been investigated in detail. RESULTS: We find that the splicing factor Caper is required for the development of multiple different mechanosensory neuron subtypes at multiple life stages in Drosophila melanogaster...
May 23, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28516569/stat4-expression-and-activation-is-increased-during-mitosis-in-vitro-and-in-vivo-in-skin-and-mucosa-derived-cell-types-implications-in-neoplastic-and-inflammatory-skin-diseases
#20
Caterina Ferreli, Chester Lai, Suzannah August, Yvonne Buggy, Pawan Kumar, Nicola Brownlow, Peter Parker, Peter S Friedmann, Michael Ardern-Jones, Chris Pickard, Eugene Healy
BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis, and is distributed throughout the cytoplasm during this stage of the cell cycle whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment...
May 18, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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