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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/27905502/immune-responsiveness-of-cd4-t-cells-during-streptococcus-suis-serotype-2-infection
#2
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/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#3
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
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
#4
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/27882144/effect-of-cyclosporin-a-intervention-on-the-immunological-mechanisms-of-coronary-heart-disease-and-restenosis
#5
Xuan Wang, Yue-Cheng Hu, Ru-Yan Zhang, Dong-Xia Jin, Yuan Jiang, He-Nan Zhang, Hong-Liang Cong
The present study aimed to investigate the effect of cyclosporin A (CSA) intervention on the immunological mechanisms underlying coronary heart disease (CHD) and restenosis (RS) in rabbits. A total of 48 rabbits were randomly divided into normal control (N), N + CSA, CHD model, CHD + CSA, RS model and RS + CSA groups. Rabbits in the respective groups received different treatments prior to sacrifice at the end of week 12. Iliac arteries were harvested from the rabbits for morphological analysis and to determine the mRNA and protein expression levels of cluster of differentiation (CD) 40/CD40 ligand (CD40L), CD134/CD134 ligand (CD134L) and inflammatory factors, including matrix metalloproteinase (MMP)-1, MMP-9, vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, by reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27879468/relationship-between-plasma-levels-of-soluble-cd40-ligand-and-the-presence-and-severity-of-isolated-coronary-artery-ectasia
#6
Cem Ozde, Ahmet Korkmaz, Harun Kundi, Ersan Oflar, Ismail Ungan, Vusal Xankisi, Nilhan Nurlu
OBJECTIVE: We aimed to investigate whether soluble CD40 ligand (CD40L) levels are higher in patients with isolated coronary artery ectasia (CAE) compared to patients with angiographically normal coronary arteries and those with stable coronary artery disease (CAD). MATERIALS AND METHODS: In all, 55 patients with isolated CAE without stenosis, 55 with stable CAD, and 55 control participants with angiographically normal coronary arteries were included. The CAE severity was determined according to the Markis classification...
November 21, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27878431/aqueous-immune-mediators-in-malignant-uveal-melanomas-in-comparison-to-benign-pigmented-intraocular-tumors
#7
Yoshihiko Usui, Kinya Tsubota, Tsuyoshi Agawa, Shunichiro Ueda, Kazuhiko Umazume, Yoko Okunuki, Takeshi Kezuka, Naoyuki Yamakawa, Hiroshi Goto
BACKGROUND: To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors. METHODS: Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L...
November 22, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27872868/minor-antigen-disparities-impede-induction-of-long-lasting-chimerism-and-tolerance-through-bone-marrow-transplantation-with-costimulation-blockade
#8
Sinda Bigenzahn, Ines Pree, Christoph Klaus, Nina Pilat, Benedikt Mahr, Elisabeth Schwaiger, Patrick Nierlich, Friedrich Wrba, Thomas Wekerle
Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB), but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2(b)) mice received nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti-CD40L mAb and CTLA4Ig), and 2 × 10(7) bone marrow cells (BMC) from either of three donor strains: Balb/c (H2(d)) (MHC plus multiple minor histocompatibility antigen (mHAg) mismatched), B10...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#9
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27861835/distinct-t-helper-cell-dependence-of-memory-b-cell-proliferation-versus-plasma-cell-differentiation
#10
Franziska Zabel, Antonia Fettelschoss, Monique Vogel, Pal Johansen, Thomas M Kündig, Martin F Bachmann
Several memory B cell subclasses with distinct functions have been described of which the most effective is the class-switched (CS) memory B cell population. We have previously shown using virus-like particles (VLPs) that the proliferative potential of these CS memory B cells is limited and they fail to re-enter GCs. However, VLP specific memory B cells quickly differentiated into secondary plasma cells (PCs) with a virtue of elevated Ab production compared to primary PCs. Whereas the induction of VLP+ memory B cells was strongly dependent on Th, we were wondering whether re-stimulation of VLP+ memory B cells and their differentiation into secondary PCs would also require Th...
November 9, 2016: Immunology
https://www.readbyqxmd.com/read/27853810/inflammation-but-not-recruitment-of-adipose-tissue-macrophages-requires-signalling-through-mac-1-cd11b-cd18-in-diet-induced-obesity-dio
#11
Dennis Wolf, Nora Bukosza, David Engel, Marjorie Poggi, Felix Jehle, Nathaly Anto Michel, Yung-Chih Chen, Christian Colberg, Natalie Hoppe, Bianca Dufner, Louis Boon, Hermann Blankenbach, Ingo Hilgendorf, Constantin von Zur Muhlen, Jochen Reinöhl, Björn Sommer, Timoteo Marchini, Mark A Febbraio, Christian Weber, Christoph Bode, Karlheinz Peter, Esther Lutgens, Andreas Zirlik
Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1(-/-)) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1(-/-) mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia...
November 17, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27837410/effect-of-cd40-cd40l-signaling-on-il-10-producing-regulatory-b-cells-in-chinese-children-with-henoch-sch%C3%A3-nlein-purpura-nephritis
#12
Baohui Yang, Xiongjun Tan, Xiao Xiong, Daoqi Wu, Gaofu Zhang, Mo Wang, Shifang Dong, Wei Liu, Haiping Yang, Qiu Li
The aim of the present study was to examine the role and mechanism of interleukin-10 (IL-10)-producing regulatory B cells (B10 cells) in the pathogenesis of Henoch-Schönlein purpura nephritis (HSPN). We examined the percentage of B10 cells, CD19(+)CD24(hi)CD38(hi) B cells, CD19(+)CD24(hi)CD27(+) B cells, Th17 cells, and T regulatory (Treg) cells within the peripheral blood mononuclear cell (PBMC) population in healthy subjects and HSP/HSPN patients. The percentage of B10 cells and CD19(+)CD24(hi)CD38(hi) B cells was reduced in HSPN patients and that of CD19(+)CD24(hi)CD27(+) B cells was decreased only in HSPN patients with hematuria and proteinuria or massive proteinuria...
November 11, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27835742/silencing-of-cd40-in%C3%A2-vivo-reduces-progression-of-experimental-atherogenesis-through-an-nf-%C3%AE%C2%BAb-mir-125b-axis-and-reveals-new-potential-mediators-in-the-pathogenesis-of-atherosclerosis
#13
Miguel Hueso, Laura De Ramon, Estanislao Navarro, Elia Ripoll, Josep M Cruzado, Josep M Grinyo, Joan Torras
BACKGROUND AND AIMS: CD40/CD40L signaling exerts a critical role in the development of atherosclerosis, and microRNAs (miRNAs) are key regulators in vascular inflammation and plaque formation. In this work, we investigated mRNA/miRNA expression during progression of atherosclerotic lesions through CD40 silencing. METHODS: We silenced CD40 with a specific siRNA in ApoE(-/-) mice and compared expression of mRNA/miRNA in ascending aorta with scrambled treated mice...
November 2, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27832278/il-17a-promotes-rantes-expression-but-not-il-16-in-orbital-fibroblasts-via-cd40-cd40l-combination-in-thyroid-associated-ophthalmopathy
#14
Sijie Fang, Yazhuo Huang, Sisi Zhong, Yidan Zhang, Xingtong Liu, Yang Wang, Ping Gu, Huifang Zhou, Xianqun Fan
Purpose: This present study aims to investigate the phenotype of IL-17A-producing T cells in thyroid-associated ophthalmopathy (TAO) and the role of IL-17A on RANTES and IL-16 expression in orbital fibroblasts (OFs) from TAO patients. Methods: Blood samples were obtained from TAO patients and healthy controls and were subjected to ELISA and flow cytometry analysis. Primary human OFs cultured from surgical wastes were stimulated with IL-17A in the presence or absence of CD40L and were examined by qRT-PCR, ELISA, Western blotting, and apoptosis assays...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27818020/ezetimibe-inhibits-platelet-activation-and-upar-expression-on-endothelial-cells
#15
Tobias Becher, Torsten J Schulze, Melanie Schmitt, Frederik Trinkmann, Ibrahim El-Battrawy, Ibrahim Akin, Thorsten Kälsch, Martin Borggrefe, Ksenija Stach
PURPOSE: Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model. METHODS: After a 24h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets...
October 3, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27817782/-recurrent-fever-hepatosplenomegaly-and-eosinophilia-in-a-boy
#16
Dan Liu, Li-Li Zhong, Yun Li, Min Chen
A 2-year-old boy was admitted into the hospital because of cough and fever. Lymph node tuberculosis was noted when he was 2 months old and he was subsequently hospitalized several times because of cough and fever. After hospitalization the laboratory examination showed an increased eosinophia level in blood. The immune function tests shows decreased levels of IgG, IgA, and IgM. The patient had no response to anti-tuberculosis, anti-bacterial, and anti-fungal treatment, resulting in recurrent fever and progressive enlargement of the liver and spleen...
November 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/27802906/platelet-mediated-modulation-of-adaptive-immunity
#17
REVIEW
Matteo Iannacone
Besides being the main cellular effectors of hemostasis, platelets possess a plethora of intracellular mediators (e.g. cytokines, chemokines and antimicrobial molecules) as well as surface receptors (e.g. P-selectin, integrins, CD40L, intercellular adhesion molecule [ICAM]-2, junctional adhesion molecule [JAM]-A, CD44, Toll-like receptors, chemokine receptors) known for their involvement in inflammatory and immune responses. These aspects of platelet biology, which suggest an evolutionary link to a more primitive multifunctional innate defensive cell, position platelets at the interface between coagulation and immunity...
October 29, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27800605/b-cell-activation-with-cd40l-or-cpg-measures-the-function-of-b-cell-subsets-and-identifies-specific-defects-in-immunodeficient-patients
#18
Emiliano Marasco, Chiara Farroni, Simona Cascioli, Valentina Marcellini, Marco Scarsella, Ezio Giorda, Eva Piano Mortari, Lucia Leonardi, Alessia Scarselli, Diletta Valentini, Caterina Cancrini, Marzia Duse, Ola Grimsholm, Rita Carsetti
Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells...
November 1, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27798262/autoimmune-manifestations-in-aged-mice-arise-from-early-life-immune-dysregulation
#19
Tamer I Mahmoud, Jingya Wang, Jodi L Karnell, Qiming Wang, Shu Wang, Brian Naiman, Phillip Gross, Philip Z Brohawn, Chris Morehouse, Jordan Aoyama, Clive Wasserfall, Laura Carter, Mark A Atkinson, David V Serreze, Helen Braley-Mullen, Tomas Mustelin, Roland Kolbeck, Ronald Herbst, Rachel Ettinger
Autoantibodies can be present years to decades before the onset of disease manifestations in autoimmunity. This finding suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which ultimately drives disease pathology in local tissues later in life. We show that Sjögren's syndrome manifestations that develop in aged NOD.H-2h4 mice were driven by and dependent on peripheral dysregulation that arose in early life. Specifically, elimination of spontaneous germinal centers in spleens of young NOD...
October 19, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27798157/cd40-mediated-nf-%C3%AE%C2%BAb-activation-in-b-cells-is-increased-in-multiple-sclerosis-and-modulated-by-therapeutics
#20
Ding Chen, Sara J Ireland, Gina Remington, Enrique Alvarez, Michael K Racke, Benjamin Greenberg, Elliot M Frohman, Nancy L Monson
CD40 interacts with CD40L and plays an essential role in immune regulation and homeostasis. Recent research findings, however, support a pathogenic role of CD40 in a number of autoimmune diseases. We previously showed that memory B cells from relapsing-remitting multiple sclerosis (RRMS) patients exhibited enhanced proliferation with CD40 stimulation compared with healthy donors. In this study, we used a multiparameter phosflow approach to analyze the phosphorylation status of NF-κB and three major MAPKs (P38, ERK, and JNK), the essential components of signaling pathways downstream of CD40 engagement in B cells from MS patients...
October 26, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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