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https://www.readbyqxmd.com/read/27919753/advax-a-delta-inulin-microparticle-potentiates-in-built-adjuvant-property-of-co-administered-vaccines
#1
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...
December 1, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27913566/th2-responses-are-primed-by-skin-dendritic-cells-with-distinct-transcriptional-profiles
#2
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...
December 2, 2016: 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
#3
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
#4
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
#5
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...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27882218/adenovirus-co-expressing-cd40-ligand-and-interleukin-il-2-contributes-to-maturation-of-dendritic-cells-and-production-of-il-12
#6
Zhi Guo, Hong-Yan Gao, Tian-Yang Zhang, Jin-Xing Lou, Kai Yang, Xiao-Dong Liu, Xue-Peng He, Hui-Ren Chen
The aim of the present study was to construct a chimeric adenovirus (Ad)5/F35 co-expressing human CD4O ligand (CD4OL) and interleukin (IL)-2 (Ad5/F35 CD40L-IL-2). The infection efficiency to human monocyte-derived dendritic cells (Mo-DCs), expression of genes, phenotype changes and IL-12 production of Mo-DC by Ad5/F35 CD40L-IL-2 were investigated. CD40L and IL-2 from total RNA extracted from human peripheral blood mononuclear cells (PBMCs) were cloned by reverse transcription-polymerase chain reaction and used to construct Ad5/F35 CD40L-IL-2...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27878306/effects-of-interleukin-1-receptor-associated-kinase%C3%A2-1-rna-interference-in-dendritic-cells-on-inflammatory-cytokine-release-and-t-cell-proliferation
#7
Yan Gao, Xuxu Xu, Juan Feng, Ying Ma, Dongming Zheng, Yiming Meng, Fengping Shan
The present study aimed to reduce the expression of interleukin-1 receptor-associated kinase 1 (IRAK-1) in dendritic cells (DCs) by RNA interference (RNAi). Subsequently, its effects on the expression of costimulatory surface molecules, the release of inflammatory cytokines, and the proliferation of T cells during the activation process of DCs, were determined. RNAi was used to silence IRAK‑1 gene expression in DCs, followed by lipopolysaccharide stimulation. Flow cytometry was then used to detect the expression levels of DC surface molecules, including cluster of differentiation (CD)86, major histocompatibility complex class II and CD40...
November 15, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27876497/hepatitis-c-virus-inhibits-cd4-t-cell-function-via-binding-to-toll-like-receptor-7
#8
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Serena Ludovisi, Mario U Mondelli, Stefania Varchetta
Toll-like receptor 7 (TLR7) is a ssRNA receptor that activates dendritic cells and macrophages upon ssRNA binding; however, little is known of its role in CD4(+) T cells. We show here that hepatitis C virus (HCV) induces a dose dependent inhibition of cytokine production and expression of activation markers in CD4 T cells, which were restored by a TLR7-specific antagonist. These findings indicate that HCV induces CD4 T cell impairment via TLR7 which may contribute to failure of virus eradication, casting doubts on the use of TLR7 agonists to boost innate immunity in chronic RNA virus infections...
November 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27852742/soluble-tnf-regulates-tace-via-ap-2%C3%AE-transcription-factor-in-mouse-dendritic-cells
#9
Lisheng Ge, Nikola L Vujanovic
Dendritic cells (DCs), the essential immunoregulatory and APCs, are major producers of the central mediator of inflammation, soluble TNF-α (sTNF). sTNF is generated by TNF-α converting enzyme (TACE) proteolytic release of the transmembrane TNF (tmTNF) ectodomain. The mechanisms of TACE and sTNF regulation in DCs remain elusive. This study newly defines that sTNF regulates TACE in mouse DCs by engaging the AP-2α transcription factor. We found that the expression of AP-2α was higher, whereas the expression and activity of TACE were lower, in wild-type DCs (wtDCs) than in TNF knockout (TNFko) DCs...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27845263/osteoclastogenic-capacity-of-peripheral-blood-mononuclear-cells-is-not-different-between-women-with-and-without-osteoporosis
#10
W N H Koek, B C J van der Eerden, R D A M Alves, M van Driel, M Schreuders-Koedam, M C Zillikens, J P T M van Leeuwen
INTRODUCTION: Peripheral Blood Mononuclear Cells (PBMCs) have been extensively used as a culture model to generate osteoclasts in vitro. The aim of this study was to assess the osteoclastogenic potential of PBMCs derived from post-menopausal women with longstanding osteoporosis and compare this with PBMCs from healthy controls. MATERIAL AND METHODS: We selected from the population-based Rotterdam Study 82 participants of which 43 were diagnosed with osteoporosis (T-score below -2...
November 12, 2016: Bone
https://www.readbyqxmd.com/read/27837108/characterization-and-transcriptomic-analysis-of-porcine-blood-conventional-and-plasmacytoid-dendritic-cells-reveals-striking-species-specific-differences
#11
Gael Auray, Irene Keller, Sylvie Python, Markus Gerber, Remy Bruggmann, Nicolas Ruggli, Artur Summerfield
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135(+)CD14(-)CD172a(low)CADM1(+)wCD11R1(+) cells, cDC2 are CD135(+)CD14(-)CD172a(+)CADM1(+)CD115(+)wCD11R1(+)CD1(+) cells and pDCs are CD4(+)CD135(+)CD172a(+)CD123(+)CD303(+) cells...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27834952/double-stranded-rna-promotes-ctl-independent-tumor-cytolysis-mediated-by-cd11b-ly6g-intratumor-myeloid-cells-through-the-ticam-1-signaling-pathway
#12
Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b(+)Ly6G(+) cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b(+)Ly6G(+) cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model...
November 11, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27832318/immunological-effects-of-a-novel-rna-based-adjuvant-in-liver-cancer-patients
#13
Luisa Circelli, Annacarmen Petrizzo, Maria Tagliamonte, Regina Heidenreich, Maria Lina Tornesello, Franco M Buonaguro, Luigi Buonaguro
Evaluation of biological effects of adjuvants on immune cells has been assessed in a limited number of studies. Moreover, no data are available on samples derived from cancer patients who may have a severe immune impairment. The effects of a novel RNA-based adjuvant (RNAdjuvant(®) developed by CureVac) were assessed in an ex vivo setting on PBMCs obtained from 8 healthy volunteers and 17 HCC patients, using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression, cytokine production as well as gene expression was performed...
November 10, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27827318/isolation-of-t-cell-receptors-specifically-reactive-with-mutated-tumor-associated-antigens-from-tumor-infiltrating-lymphocytes-based-on-cd137-expression
#14
Maria R Parkhurst, Alena Gros, Anna Pasetto, Todd D Prickett, Jessica S Crystal, Paul F Robbins, Steven A Rosenberg
PURPOSE: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T cell receptors (TCRs) can mediate tumor regression. Some tumor infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TIL target tumor specific neoantigens. Here we attempted to isolate neoantigen reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27824109/thymic-exosomes-promote-the-final-maturation-of-thymocytes
#15
Vanja Lundberg, Martin Berglund, Gabriel Skogberg, Susanne Lindgren, Christina Lundqvist, Judith Gudmundsdottir, Karolina Thörn, Esbjörn Telemo, Olov Ekwall
Extensive knowledge has been gained the last years concerning mechanisms underlying the selection of single positive thymocytes in the thymic medulla. Less is known regarding other important processes in the thymic medulla such as the regulation of late stage thymocyte maturation. We have previously reported that exosomes are abundant in the thymus with a phenotype that indicates an epithelial cell origin and immunoregulatory properties. In this study we use an in vitro system to investigate the effects of thymic exosomes on the maturation of single positive thymocytes as well as effects on nTreg formation...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822498/the-x-linked-autism-protein-kiaa2022-kidlia-regulates-neurite-outgrowth-via-n-cadherin-and-%C3%AE-catenin-signaling
#16
James Gilbert, Heng-Ye Man
Our previous work showed that loss of the KIAA2022 gene protein results in intellectual disability with language impairment and autistic behavior (KIDLIA, also referred to as XPN). However, the cellular and molecular alterations resulting from a loss of function of KIDLIA and its role in autism with severe intellectual disability remain unknown. Here, we show that KIDLIA plays a key role in neuron migration and morphogenesis. We found that KIDLIA is distributed exclusively in the nucleus. In the developing rat brain, it is expressed only in the cortical plate and subplate region but not in the intermediate or ventricular zone...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27816055/genome-wide-profiling-of-chicken-dendritic-cell-response-to-infectious-bursal-disease
#17
Jian Lin, Jing Xia, Keyun Zhang, Qian Yang
BACKGROUND: Avian infectious bursal disease virus (IBDV) is a highly contagious, immunosuppressive disease of young chickens, which causes high mortality rates and large economic losses in the poultry industry. Dendritic cells (DCs), which are antigen-presenting cells, have the unique ability to induce both innate and acquired immune responses and may significantly influence virus pathogenicity. To understand the interaction between IBDV and DCs, a microarray was used to analyse the response of DCs infected by IBDV...
November 5, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27815426/gata1-deficient-dendritic-cells-display-impaired-ccl21-dependent-migration-toward-lymph-nodes-due-to-reduced-levels-of-polysialic-acid
#18
Maaike R Scheenstra, Iris M De Cuyper, Filipe Branco-Madeira, Pieter de Bleser, Mirjam Kool, Marjolein Meinders, Mark Hoogenboezem, Erik Mul, Monika C Wolkers, Fiamma Salerno, Benjamin Nota, Yvan Saeys, Sjoerd Klarenbeek, Wilfred F J van IJcken, Hamida Hammad, Sjaak Philipsen, Timo K van den Berg, Taco W Kuijpers, Bart N Lambrecht, Laura Gutiérrez
Dendritic cells (DCs) play a pivotal role in the regulation of the immune response. DC development and activation is finely orchestrated through transcriptional programs. GATA1 transcription factor is required for murine DC development, and data suggest that it might be involved in the fine-tuning of the life span and function of activated DCs. We generated DC-specific Gata1 knockout mice (Gata1-KO(DC)), which presented a 20% reduction of splenic DCs, partially explained by enhanced apoptosis. RNA sequencing analysis revealed a number of deregulated genes involved in cell survival, migration, and function...
November 4, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27812247/chronic-myelocytic-leukemia-cml-patient-derived-dendritic-cells-transfected-with-autologous-total-rna-induces-cml-specific-cytotoxicity
#19
Li Yu, Ting Hu, Tian Zou, Qingzhi Shi, Guoan Chen
The oncogenic bcr/abl1 fusion gene is a chronic myelogenous leukemia (CML)-specific antigen which is absent in normal tissues. This makes bcr/abl1 a perfect target for developing CML vaccines that elicit specific immune responses against minimal residual disease while sparing normal tissue. The aim of this study was to use different methods to induce dendritic cells (DCs) derived from patients with CML (CML-DCs) and analyze them for CML-specific tumor cytotoxicity for immune therapy. Bone marrow-derived mononuclear cells from ten CML patients were studied to induce CML-DC differentiation in the presence of recombinant human interleukin-4, rh-granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor-alpha with either a total RNA-lipofectamine complex, total RNA or CML tumor lysate (freeze-thawed)...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27803478/development-of-a-drug-delivery-system-for-cancer-immunotherapy
#20
Takashi Nakamura
 Delivery systems are a powerful technology for enhancing the effect of cancer immunotherapy. We have been in the process of developing lipid-based delivery systems for controlling the physical properties and dynamics of immunofunctional molecules such as antigens and adjuvants. The lipid nanoparticulation of these molecules improves their physical properties, resulting in a good water dispensability, greater stability, and small size. The cell wall skeleton of bacille Calmette-Guerin (BCG-CWS) could be used to replace live BCG as a drug for treating bladder cancer, but problems associated with the physical properties of BCG-CWS have prevented its use...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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