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https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#1
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27906000/the-antiviral-compound-bit225-inhibits-hiv-1-replication-in-myeloid-dendritic-cells
#2
Gabriela Khoury, Gary Ewart, Carolyn Luscombe, Michelle Miller, John Wilkinson
BACKGROUND: Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies...
February 8, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905610/dendritic-polyglycerol-and-n-isopropylacrylamide-based-thermoresponsive-nanogels-as-smart-carriers-for-controlled-delivery-of-drugs-through-the-hair-follicle
#3
Fitsum Feleke Sahle, Michael Giulbudagian, Julian Bergueiro, Jürgen Lademann, Marcelo Calderón
Nanoparticles with a size of several hundred nanometers can effectively penetrate into the hair follicles and may serve as depots for controlled drug delivery. However, they can neither overcome the hair follicle barrier to reach the viable cells nor release the loaded drug adequately. On the other hand, small drug molecules cannot penetrate deep into the hair follicles. Thus, the most efficient way for drug delivery through the follicular route is to employ nanoparticles that can release the drug close to the target structure upon exposure to some external or internal stimuli...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27905502/immune-responsiveness-of-cd4-t-cells-during-streptococcus-suis-serotype-2-infection
#4
Marie-Pier Lecours, Corinne Letendre, Damian Clarke, Paul Lemire, Tristan Galbas, Marie-Odile Benoit-Biancamano, Jacques Thibodeau, Marcelo Gottschalk, Mariela Segura
The pathogenesis of Streptococcus suis infection, a major swine and human pathogen, is only partially understood and knowledge on the host adaptive immune response is critically scarce. Yet, S. suis virulence factors, particularly its capsular polysaccharide (CPS), enable this bacterium to modulate dendritic cell (DC) functions and potentially impair the immune response. This study aimed to evaluate modulation of T cell activation during S. suis infection and the role of DCs in this response. S. suis-stimulated total mouse splenocytes readily produced TNF-α, IL-6, IFN-γ, CCL3, CXCL9, and IL-10...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905484/independent-control-of-natural-killer-cell-responsiveness-and-homeostasis-at-steady-state-by-cd11c-dendritic-cells
#5
Thuy Thanh Luu, Sridharan Ganesan, Arnika Kathleen Wagner, Dhifaf Sarhan, Stephan Meinke, Natalio Garbi, Günter Hämmerling, Evren Alici, Klas Kärre, Benedict J Chambers, Petter Höglund, Nadir Kadri
During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905296/a-pathogenic-role-for-the-integrin-cd103-in-experimental-allergic-airways-disease
#6
Vanessa S Fear, Siew Ping Lai, Graeme R Zosky, Kara L Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A Stumbles, Deborah H Strickland
The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#7
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
November 7, 2016: Immunology
https://www.readbyqxmd.com/read/27905000/decidual-natural-killer-cells-and-the-immune-microenvironment-at-the-maternal-fetal-interface
#8
REVIEW
Binqing Fu, Haiming Wei
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56(bright)CD16(-) phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy...
November 29, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27904822/targeted-sequencing-approach-to-identify-genetic-mutations-in-nasu-hakola-disease
#9
Jun-Ichi Satoh, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Yoshihiro Kino
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Premortem molecular diagnosis of NHD requires genetic analysis of both TYROBP and TREM2, in which 20 distinct NHD-causing mutations have been reported. Due to genetic heterogeneity, it is often difficult to identify the exact mutation responsible for NHD...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#10
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903882/cap-analogs-modified-with-1-2-dithiodiphosphate-moiety-protect-mrna-from-decapping-and-enhance-its-translational-potential
#11
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/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#12
Patricia U Simioni, Luis Gr Fernandes, Wirla Msc Tamashiro
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11...
November 30, 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27903737/allergen-induced-cd4-t-cell-cytokine-production-within-airway-mucosal-dendritic-cell-t-cell-clusters-drives-the-local-recruitment-of-myeloid-effector-cells
#13
Tibor Z Veres, Tamás Kopcsányi, Nicholas van Panhuys, Michael Y Gerner, Zhiduo Liu, Pia Rantakari, Johannes Dunkel, Masayuki Miyasaka, Marko Salmi, Sirpa Jalkanen, Ronald N Germain
Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4(+) T cells formed discrete Ag-driven clusters with dendritic cells (DCs)...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27903432/antigen-presentation-for-priming-t-cellsin-central-system
#14
Shaoni Dasgupta, Subhajit Dasgupta
Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system...
November 26, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27902915/characterization-of-chicken-splenic-derived-dendritic-cells-following-vaccine-and-very-virulent-strains-of-infectious-bursal-disease-virus-infection
#15
A R Yasmin, S K Yeap, M Hair-Bejo, A R Omar
Studies have shown that infectious bursal disease virus (IBDV) infects lymphoid cells, mainly B cells and macrophages. This study was aimed to examine the involvement of chicken splenic-derived dendritic cells (ch-sDCs) in specific-pathogen-free chickens following inoculation with IBDV vaccine strain (D78) and a very virulent (vv) strain (UPM0081). Following IBDV infection, enriched activated ch-sDCs were collected by using the negative selection method and were examined based on morphology and immunophenotyping to confirm the isolation method for dendritic cells (DCs)...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902420/interleukin-1-receptor-antagonist-il-1ra-an-early-immunomodulatory-cytokine-induced-by-porcine-reproductive-and-respiratory-syndrome-virus-prrsv
#16
Teerawut Nedumpun, Piya Wongyanin, Chaitawat Sirisereewan, Patcharee Ritprajuk, Tanapat Palaga, Roongroje Thanawongnuwech, Sanipa Suradhat
Porcine reproductive and respiratory syndrome virus (PRRSV) infection poorly induces pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and type I IFN production during the early phase of infection. Our microarray analysis indicated strong upregulation of the IL1RA gene in type 2 PRRSV infected monocyte-derived dendritic cells (MoDC). Interleukin-1 receptor antagonist (IL-1Ra) is an early inhibitory cytokine, which suppresses pro-inflammatory cytokines and T lymphocyte responses. To investigate the induction of IL-1Ra by PRRSV, MoDC were cultured with type 2 PRRSV or other swine viruses...
November 23, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902338/recombinant-rabies-virus-expressing-il-21-enhances-immunogenicity-through-activation-of-t-follicular-helper-cells-and-germinal-center-b-cells
#17
Yajing Zhang, Ming Zhou, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signaling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated as LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that mice immunized with LBNSE-IL21 could substantially increase the number of T follicular helper (Tfh) cells and germinal center (GC) B cells but did not enhance dendritic cell (DC) activation...
October 25, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#18
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/27901063/regulation-of-%C3%AE-2b-adrenergic-receptor-cell-surface-transport-by-gga1-and-gga2
#19
Maoxiang Zhang, Wei Huang, Jie Gao, Alvin V Terry, Guangyu Wu
The molecular mechanisms that control the targeting of newly synthesized G protein-coupled receptors (GPCRs) to the functional destinations remain poorly elucidated. Here, we have determined the role of Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding proteins 1 and 2 (GGA1 and GGA2) in the cell surface transport of α2B-adrenergic receptor (α2B-AR), a prototypic GPCR, and studied the underlying mechanisms. We demonstrated that knockdown of GGA1 and GGA2 by shRNA and siRNA significantly reduced the cell surface expression of inducibly expressed α2B-AR and arrested the receptor in the perinuclear region...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900517/erratum-to-pulsed-dendritic-cells-for-the-therapy-of-experimental-glioma
#20
I V Chekhonin, O I Gurina, S A Cherepanov, M A Abakumov, K P Ionova, D I Zhigarev, A V Makarov, V P Chekhonin
No abstract text is available yet for this article.
November 29, 2016: Bulletin of Experimental Biology and Medicine
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