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https://www.readbyqxmd.com/read/28096318/bone-marrow-mesenchymal-stem-cells-inhibit-dendritic-cells-differentiation-and-maturation-by-microrna-23b
#1
Jingguo Wu, Chengbo Ji, Qingwei Jia, Feifei Cao, Yong Li, Xishan Zhang, Lanping Wang
BACKGROUND AND AIMS: Research on regulation and its mechanism of bone marrow mesenchymal stem cells (BMSCs) on dendritic cells (DCs) which is the initiating factor in immune response has applicable clinical value. Although BMSCs have a significant regulatory effect on the maturation of DCs, its molecular mechanism is still unclear. METHODS: Isolation and culture of BMSCs and DCs, they were co-cultured in different proportions. Flow cytometry was used to detect the expression of DCs markers (CD83, CD11c)...
January 17, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#2
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28077601/a-new-rna-based-adjuvant-enhances-virus-specific-vaccine-responses-by-locally-triggering-tlr-and-rlh-dependent-effects
#3
Annett Ziegler, Claudia Soldner, Stefan Lienenklaus, Julia Spanier, Stephanie Trittel, Peggy Riese, Thomas Kramps, Siegfried Weiss, Regina Heidenreich, Edith Jasny, Carlos A Guzmán, Karl-Josef Kallen, Mariola Fotin-Mleczek, Ulrich Kalinke
Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28056059/high-levels-of-ebv-encoded-rna-1-eber1-trigger-interferon-and-inflammation-related-genes-in-keratinocytes-expressing-hpv16-e6-e7
#4
Sirinart Aromseree, Jaap M Middeldorp, Chamsai Pientong, Monique van Eijndhoven, Octavia Ramayanti, Sinéad M Lougheed, D Michiel Pegtel, Renske D M Steenbergen, Tipaya Ekalaksananan
Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal layer of cervical lesions. In this study, we aimed to determine effects of exosome-transferred EBV-encoded RNAs (EBERs) on keratinocytes expressing human papillomavirus (HPV) 16 E6/E7 (DonorI-HPV16 HFKs). Lipid transfection of in vitro-transcribed EBER1 molecules (ivt EBER1) into DonorI-HPV16 HFKs caused strong induction of interferon (IFN)-related genes and interleukin 6 (IL-6)...
2017: PloS One
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#5
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/28009273/life-at-low-copy-number-how-dendrites-manage-with-so-few-mrnas
#6
REVIEW
Kenneth S Kosik
Most mammalian dendrites have surprisingly few copy numbers of mRNAs relative to the large number of synapses and consequently, at any given moment, the majority of synapses do not have a repertoire of mRNAs within their immediate locale capable of initiating translation-dependent plasticity. The dimensions of the translationally serviceable locale around synapses have boundary parameters that can be estimated. When a synapse receives an input beyond that boundary, the requisite mRNAs for local translation and plasticity may not be there...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/28008823/saccharomyces-boulardii-improves-humoral-immune-response-to-dna-vaccines-against-leptospirosis
#7
Marcelle Moura Silveira, Fabricio Conceição, Marcelo Mendonça, Carlos Eduardo Da Cunha, Gustavo Moreira, Neida Conrad, Patrícia Oliveira, Daiane Hartwig, Priscila De Leon, Ângela Moreira
Saccharomyces boulardii may improve the immune response by enhancing the production of anti-inflammatory cytokines, T cell proliferation and dendritic cell activation. The immunomodulator effect of this probiotic has never been tested with DNA vaccines, which frequently induce low antibody titers. This study evaluated Saccharomyces boulardii capacity to improve the humoral and cellular immune responses using DNA vaccines coding for the leptospiral protein fragments LigAni and LigBrep. BALB/c mice were fed with rodent-specific feed containing 108 colony-forming units of Saccharomyces boulardii per gram...
December 22, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28008810/a-polysaccharide-from-the-culinary-medicinal-mushroom-pholiota-nameko-agaricomycetes-inhibits-the-nf-%C3%AE%C2%BAb-pathway-in-dendritic-cells-through-the-tlr2-receptor
#8
Haiping Li, Pei Zhao, Fengling Wang, Lihua Huai, Ruixuan Zhu, Guoliang Li, Yufeng Xu
A polysaccharide purified from Pholiota nameko (PNPS-1) was found to have anticancer and anti-inflammatory activity. This study investigated the effect of PNPS-1 on the nuclear factor (NF)-κB signaling pathway of TLR2 small interfering RNA-silenced murine bone marrow-derived dendritic cells (BMDCs) and relevant mechanisms. The expression of messenger RNA of 4 NF-κB-related genes, including MyD88, IKBKB, RelA(p65), and CCL2, was determined by real-time polymerase chain reaction; the expression of the phenotype molecule intercellular adhesion molecule-1 (ICAM-1) by flow cytometry; the protein expression of IKKβ and p65 by Western blot; the production of p65 by enzyme-linked immunosorbent assay; and the expression of p65 by immunocytochemistry...
2016: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28007914/a-reverse-signaling-pathway-downstream-of-sema4a-controls-cell-migration-via-scrib
#9
Tianliang Sun, Lida Yang, Harmandeep Kaur, Jenny Pestel, Mario Looso, Hendrik Nolte, Cornelius Krasel, Daniel Heil, Ramesh K Krishnan, Marie-Josée Santoni, Jean-Paul Borg, Moritz Bünemann, Stefan Offermanns, Jakub M Swiercz, Thomas Worzfeld
Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28007091/inhibition-effect-of-blunting-notch-signaling-on-food-allergy-through-improving-th1-th2-balance-in-mice
#10
Songsong Jiang, Shiwen Han, Jingyu Chen, Xuejiao Li, Huilian Che
BACKGROUND: Notch signaling regulates proliferation, differentiation, and function of dendritic cells, T cells, and mast cells, as well as many other immune cells, which act as important parts in food allergy, Notch signaling may play an important role in food allergy. OBJECTIVE: To investigate the role of Notch signaling in IgE-mediated food allergy. METHODS: An ovalbumin-induced food allergy mouse model was built (cholera toxin as adjuvant) and Notch signaling was blunted by FLI-06 and MW167, which inhibited Notch receptor-expressing phase and the γ-secretase-affecting phase, respectively...
January 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27999747/immune-response-and-long-term-clinical-outcome-in-advanced-melanoma-patients-vaccinated-with-tumor-mrna-transfected-dendritic-cells
#11
Jon Amund Kyte, Steinar Aamdal, Svein Dueland, Stein Sæbøe-Larsen, Else Marit Inderberg, Ulf Erik Madsbu, Eva Skovlund, Gustav Gaudernack, Gunnar Kvalheim
The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27987142/self-replicating-rna-vaccine-delivery-to-dendritic-cells
#12
Thomas Démoulins, Pavlos C Englezou, Panagiota Milona, Nicolas Ruggli, Nicola Tirelli, Chantal Pichon, Cédric Sapet, Thomas Ebensen, Carlos A Guzmán, Kenneth C McCullough
Most current vaccines are either inactivated pathogen-derived or protein/peptide-based, although attenuated and vector vaccines have also been developed. The former induce at best moderate protection, even as multimeric antigen, due to limitations in antigen loads and therefore capacity for inducing robust immune defense. While attenuated and vector vaccines offer advantages through their replicative nature, drawbacks and risks remain with potential reversion to virulence and interference from preexisting immunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27984734/dissecting-immune-circuits-by-linking-crispr-pooled-screens-with-single-cell-rna-seq
#13
Diego Adhemar Jaitin, Assaf Weiner, Ido Yofe, David Lara-Astiaso, Hadas Keren-Shaul, Eyal David, Tomer Meir Salame, Amos Tanay, Alexander van Oudenaarden, Ido Amit
In multicellular organisms, dedicated regulatory circuits control cell type diversity and responses. The crosstalk and redundancies within these circuits and substantial cellular heterogeneity pose a major research challenge. Here, we present CRISP-seq, an integrated method for massively parallel single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-pooled screens. We show that profiling the genomic perturbation and transcriptome in the same cell enables us to simultaneously elucidate the function of multiple factors and their interactions...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27984732/perturb-seq-dissecting-molecular-circuits-with-scalable-single-cell-rna-profiling-of-pooled-genetic-screens
#14
Atray Dixit, Oren Parnas, Biyu Li, Jenny Chen, Charles P Fulco, Livnat Jerby-Arnon, Nemanja D Marjanovic, Danielle Dionne, Tyler Burks, Raktima Raychowdhury, Britt Adamson, Thomas M Norman, Eric S Lander, Jonathan S Weissman, Nir Friedman, Aviv Regev
Genetic screens help infer gene function in mammalian cells, but it has remained difficult to assay complex phenotypes-such as transcriptional profiles-at scale. Here, we develop Perturb-seq, combining single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations to perform many such assays in a pool. We demonstrate Perturb-seq by analyzing 200,000 cells in immune cells and cell lines, focusing on transcription factors regulating the response of dendritic cells to lipopolysaccharide (LPS)...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27959965/functional-analyses-of-the-crohn-s-disease-risk-gene-lacc1
#15
Ghazaleh Assadi, Liselotte Vesterlund, Ferdinando Bonfiglio, Luca Mazzurana, Lina Cordeddu, Danika Schepis, Jenny Mjösberg, Sabrina Ruhrmann, Alessia Fabbri, Vladana Vukojevic, Piergiorgio Percipalle, Florian A Salomons, Jurga Laurencikiene, Leif Törkvist, Jonas Halfvarson, Mauro D'Amato
BACKGROUND: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression...
2016: PloS One
https://www.readbyqxmd.com/read/27919753/advax-a-delta-inulin-microparticle-potentiates-in-built-adjuvant-property-of-co-administered-vaccines
#16
Masayuki Hayashi, Taiki Aoshi, Yasunari Haseda, Kouji Kobiyama, Edward Wijaya, Noriyuki Nakatsu, Yoshinobu Igarashi, Daron M Standley, Hiroshi Yamada, Yoshikazu Honda-Okubo, Hiromitsu Hara, Takashi Saito, Toshiyuki Takai, Cevayir Coban, Nikolai Petrovsky, Ken J Ishii
Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27913566/th2-responses-are-primed-by-skin-dendritic-cells-with-distinct-transcriptional-profiles
#17
Lisa M Connor, Shiau-Choot Tang, Emmanuelle Cognard, Sotaro Ochiai, Kerry L Hilligan, Samuel I Old, Christophe Pellefigues, Ruby F White, Deepa Patel, Adam Alexander T Smith, David A Eccles, Olivier Lamiable, Melanie J McConnell, Franca Ronchese
The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27903882/cap-analogs-modified-with-1-2-dithiodiphosphate-moiety-protect-mrna-from-decapping-and-enhance-its-translational-potential
#18
Malwina Strenkowska, Renata Grzela, Maciej Majewski, Katarzyna Wnek, Joanna Kowalska, Maciej Lukaszewicz, Joanna Zuberek, Edward Darzynkiewicz, Andreas N Kuhn, Ugur Sahin, Jacek Jemielity
Along with a growing interest in mRNA-based gene therapies, efforts are increasingly focused on reaching the full translational potential of mRNA, as a major obstacle for in vivo applications is sufficient expression of exogenously delivered mRNA. One method to overcome this limitation is chemically modifying the 7-methylguanosine cap at the 5' end of mRNA (m(7)Gppp-RNA). We report a novel class of cap analogs designed as reagents for mRNA modification. The analogs carry a 1,2-dithiodiphosphate moiety at various positions along a tri- or tetraphosphate bridge, and thus are termed 2S analogs...
November 16, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#19
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27889761/cilostazol-suppresses-il-23-production-in-human-dendritic-cells-via-an-ampk-dependent-pathway
#20
Quanxing Shi, Zhao Yin, Peilin Liu, Bei Zhao, Zhong Zhang, Shuai Mao, Tengfei Wei, Mengmeng Rao, Liguo Zhang, Shouli Wang
BACKGROUND/AIMS: Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. METHODS: Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan...
2016: Cellular Physiology and Biochemistry
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