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CD40 Ligand

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https://www.readbyqxmd.com/read/29129918/intratumoral-cd40-activation-and-checkpoint-blockade-induces-t-cell-mediated-eradication-of-melanoma-in-the-brain
#1
Manisha Singh, Christina Vianden, Mark J Cantwell, Zhimin Dai, Zhilan Xiao, Meenu Sharma, Hiep Khong, Ashvin R Jaiswal, Faisal Faak, Yared Hailemichael, L M E Janssen, Uddalak Bharadwaj, Michael A Curran, Adi Diab, Roland L Bassett, David J Tweardy, Patrick Hwu, Willem W Overwijk
CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8(+) T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8(+) T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127283/environmental-sensing-by-mature-b-cells-is-controlled-by-the-transcription-factors-pu-1-and-spib
#2
Simon N Willis, Julie Tellier, Yang Liao, Stephanie Trezise, Amanda Light, Kristy O'Donnell, Lee Ann Garrett-Sinha, Wei Shi, David M Tarlinton, Stephen L Nutt
Humoral immunity requires B cells to respond to multiple stimuli, including antigen, membrane and soluble ligands, and microbial products. Ets family transcription factors regulate many aspects of haematopoiesis, although their functions in humoral immunity are difficult to decipher as a result of redundancy between the family members. Here we show that mice lacking both PU.1 and SpiB in mature B cells do not generate germinal centers and high-affinity antibody after protein immunization. PU.1 and SpiB double-deficient B cells have a survival defect after engagement of CD40 or Toll-like receptors (TLR), despite paradoxically enhanced plasma cell differentiation...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29115560/identification-of-key-genes-transcription-factors-and-micrornas-involved-in-intracranial-aneurysm
#3
Liang Wei, Qi Wang, Yanfei Zhang, Cheng Yang, Hongxin Guan, Yiming Chen, Zhiyang Sun
Intracranial aneurysm (IA) is a devastating disease, the pathogenesis of which remains to be elucidated. The present study aimed to determine the molecular mechanism of IA and to identify potential therapeutic targets using bioinformatics analysis. The GSE54083 dataset, which includes data from patients with ruptured IA and superficial temporal artery controls, was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) were identified in the ruptured IA samples using the limma package in R...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114094/association-of-osteopontin-neopterin-and-myeloperoxidase-with-stroke-risk-in-patients-with-prior-stroke-or-transient-ischemic-attacks-results-of-an-analysis-of-13-biomarkers-from-the-stroke-prevention-by-aggressive-reduction-in-cholesterol-levels-trial
#4
Peter Ganz, Pierre Amarenco, Larry B Goldstein, Henrik Sillesen, Weihang Bao, Gregory M Preston, K Michael A Welch
BACKGROUND AND PURPOSE: Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. METHODS: We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes...
November 7, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29108250/local-irradiation-does-not-enhance-the-effect-of-immunostimulatory-adcd40l-gene-therapy-combined-with-low-dose-cyclophosphamide-in-melanoma-patients
#5
Sandra Irenaeus, Aglaia Schiza, Sara M Mangsbo, Jessica Wenthe, Emma Eriksson, Johan Krause, Anders Sundin, Håkan Ahlström, Thomas H Tötterman, Angelica Loskog, Gustav J Ullenhag
Background: AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy. Methods: AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29089071/-whole-glucan-particle-promotes-the-maturation-of-tumor-educated-mouse-dendritic-cells-to-suppress-regulatory-t-cell-differentiation
#6
Yu Bai, Yongling Ning, Hong Zhou, Chunjian Qi
Objective To investigate the maturation and immune responses of tumor-educated dendritic cells (TEDCs) stimulated by whole glucan particle (WGP). Methods Mouse bone marrow-derived dendritic cells were generated by Flt3 ligand and co-cultured with interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in vitro to induce TEDCs, and then stimulated by WGP for 2 days. CD4(+) FOXP3(+) T cells from the lymph nodes and spleens of OT-II mice were purified by magnetic-activated cell sorting, and then co-cultured with TEDCs in the presence of ovalbumin (OVA)...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29071111/impact-of-pioglitazone-and-bradykinin-type-1-receptor-antagonist-on-type-2-diabetes-in-high-fat-diet-fed-c57bl-6j-mice
#7
S El Akoum, Y Haddad, R Couture
AIM: Type 2 diabetes (T2D) is a major complication of obesity and a leading cause of morbidity and mortality. Antagonizing bradykinin type 1 receptor (B1R) improved body and tissue fat mass and reversed vascular and adipose tissue inflammation in a rat model of insulin resistance. This study aimed at evaluating further the role of B1R in a mouse model of T2D by comparing the antidiabetic and anti-inflammatory effects of the B1R antagonist SSR240612 (SSR) in adipose tissue with those of pioglitazone (TZD), an activator of peroxisome proliferator-activated receptor gamma...
September 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29068360/soluble-cd40-ligand-and-oxidative-response-are-reciprocally-stimulated-during-shiga-toxin-associated-hemolytic-uremic-syndrome
#8
Maria J Abrey Recalde, Romina S Alvarez, Fabiana Alberto, Maria P Mejias, Maria V Ramos, Romina J Fernandez Brando, Andrea C Bruballa, Ramon A Exeni, Laura Alconcher, Cristina A Ibarra, María M Amaral, Marina S Palermo
Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types...
October 25, 2017: Toxins
https://www.readbyqxmd.com/read/29052524/soluble-cd40l-is-associated-with-increased-oxidative-burst-and-neutrophil-extracellular-trap-release-in-beh%C3%A3-et-s-disease
#9
Sandro Félix Perazzio, Paulo Vitor Soeiro-Pereira, Viviane Cardoso Dos Santos, Marlon Vilela de Brito, Bruno Salu, Maria Luiza Vilela Oliva, Anne Margherite Stevens, Alexandre Wagner Silva de Souza, Hans D Ochs, Troy R Torgerson, Antonio Condino-Neto, Luis Eduardo Coelho Andrade
BACKGROUND: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behçet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized. In this study, we sought to investigate the role of plasma and the CD40L pathway on NET release and the oxidative burst profile in patients with aBD and iBD...
October 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29040064/strong-impact-on-plasma-protein-profiles-by-precentrifugation-delay-but-not-by-repeated-freeze-thaw-cycles-as-analyzed-using-multiplex-proximity-extension-assays
#10
Qiujin Shen, Johan Björkesten, Joakim Galli, Daniel Ekman, John Broberg, Niklas Nordberg, Annika Tillander, Masood Kamali-Moghaddam, Gunnel Tybring, Ulf Landegren
Background A number of factors regarding blood collection, handling and storage may affect sample quality. The purpose of this study was to assess the impact on plasma protein profiles by delayed centrifugation and plasma separation and multiple freeze-thaw cycles. Methods Blood samples drawn from 16 healthy individuals were collected into ethylenediaminetetraacetic acid tubes and kept either at 4 °C or 22 °C for 1-36 h prior to centrifugation. Plasma samples prepared 1 h after venipuncture were also subjected to two to eight cycles of freezing at -80 °C and thawing at 22 °C...
October 17, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29038485/a-versatile-pretargeting-approach-for-tumour-selective-delivery-and-activation-of-tnf-superfamily-members
#11
Yuan He, Peter E van Bommel, Douwe F Samplonius, Edwin Bremer, Wijnand Helfrich
TNFR superfamily (TNFRSF) members have important immunoregulatory functions and are of clear interest for cancer immunotherapy. Various TNFRSF agonists have been clinically evaluated, but have met with limited efficacy and/or toxicity. Recent insights indicate that 'first-generation' TNFRSF agonists lack efficacy as they do not effectively cross-link their corresponding receptor. Reversely, ubiquitous TNFRSF receptor(s) cross-linking by CD40 and Fas agonistic antibodies resulted in dose-limiting liver toxicity...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29036612/cd40l-controls-obesity-associated-vascular-inflammation-oxidative-stress-and-endothelial-dysfunction-in-mice-translational-aspects-for-man
#12
Sebastian Steven, Mobin Dib, Michael Hausding, Fatemeh Kashani, Matthias Oelze, Swenja Kröller-Schön, Alina Hanf, Steffen Daub, Siyer Roohani, Yves Gramlich, Esther Lutgens, Eberhard Schulz, Christian Becker, Karl J Lackner, Hartmut Kleinert, Christoph Knosalla, Beate Niesler, Philipp S Wild, Thomas Münzel, Andreas Daiber
Aims: CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and Results: Male wild type and CD40L-/- mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed...
September 26, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29027839/ephb-receptors-mainly-ephb3-contribute-to-the-proper-development-of-cortical-thymic-epithelial-cells
#13
Sara Montero-Herradón, Javier García-Ceca, Agustín G Zapata
EphB and their ligands ephrin-B are an important family of protein tyrosine kinase receptors involved in thymocyte-thymic epithelial cell interactions known to be key for the maturation of both thymic cell components. In the present study, we have analyzed the maturation of cortical thymic epithelium in EphB-deficient thymuses evaluating the relative relevance of EphB2 and EphB3 in the process. Results support a relationship between the epithelial hypocellularity of mutant thymuses and altered development of thymocytes, lower proportions of cycling thymic epithelial cells and increased epithelial cell apoptosis...
October 2, 2017: Organogenesis
https://www.readbyqxmd.com/read/29023539/despite-disorganized-synapse-structure-th2-cells-maintain-directional-delivery-of-cd40l-to-antigen-presenting-b-cells
#14
Jennifer L Gardell, David C Parker
Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help...
2017: PloS One
https://www.readbyqxmd.com/read/28974444/expression-purification-and-functional-analysis-of-an-antigen-targeting-fusion-protein-composed-of-cd40-ligand-and-the-c-terminal-fragment-of-ovalbumin
#15
Yunnuo Shi, Scott A Halperin, Song F Lee
Delivering antigen via molecules specifically targeting receptors on the surface of antigen-presenting cells is a strategy to improve immune responses. In this study, an antigen-targeting fusion protein (OVA-CD40LS) composed of the C-terminal fragment of ovalbumin and the extracellular domain of mouse CD40 ligand was constructed by genetic fusion. The OVA-CD40LS and the control OVA (rOVA) genes were cloned in Escherichia coli and over-expressed as insoluble proteins. The rOVA protein was purified from the insoluble fraction of E...
September 30, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28971904/cd40-signaling-instructs-chronic-lymphocytic-leukemia-cells-to-attract-monocytes-via-the-ccr2-axis
#16
Martijn H A van Attekum, Jaco A C van Bruggen, Erik Slinger, M Cristina Lebre, Emilie Reinen, Sabina Kersting, Eric Eldering, Arnon P Kater
Chronic lymphocytic leukemia cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, chronic lymphocytic leukemia cells engage in various interactions with bystander cells such as T cells and macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be tumor supportive (M2) or play a role in tumor immune surveillance (M1). Although recent in vitro findings suggest a protective role for macrophages in chronic lymphocytic leukemia, the actual balance between these macrophage subsets in chronic lymphocytic leukemia lymphoid tissue is still unclear...
September 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28964662/replacement-therapy-with-levothyroxine-modulates-platelet-activation-in-recent-onset-post-thyroidectomy-subclinical-hypothyroidism
#17
RANDOMIZED CONTROLLED TRIAL
G Desideri, R Bocale, A D'Amore, S Necozione, M Boscherini, G Carnassale, A Barini, A Barini, R Bellantone, C P Lombardi
BACKGROUND AND AIM: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy...
October 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28958808/human-innate-responses-and-adjuvant-activity-of-tlr-ligands-in-vivo-in-mice-reconstituted-with-a-human-immune-system
#18
Liang Cheng, Zheng Zhang, Guangming Li, Feng Li, Li Wang, Liguo Zhang, Sandra M Zurawski, Gerard Zurawski, Yves Levy, Lishan Su
TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro...
October 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28904313/immune-receptors-cd40-and-cd86-in-oral-keratinocytes-and-implications-for-oral-lichen-planus
#19
Alison Marshall, Antonio Celentano, Nicola Cirillo, Michiko Mirams, Michael McCullough, Stephen Porter
Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28890720/porcine-b-cell-subset-responses-to-toll-like-receptor-ligands
#20
Roman Othmar Braun, Sylvie Python, Artur Summerfield
Toll-like receptors (TLR) triggering of B cells are known to promote B cell expansion, differentiation of B cells into antibody-producing and memory cells, but the TLR responses of porcine B cells is poorly characterized. Therefore, this study investigated the response pattern of porcine B cell subsets to a large collection of TLR ligands and demonstrates that the TLR2 ligand Pam3Cys-SK4 and the TLR7/8 ligands gardiquimod and resiquimod are particularly efficient at inducing proliferation, CD25 and CCR7. This activation was also determined in B-cell subpopulations including a CD21(+)IgM(+) subset, an IgG(+) subset and two putative B1-like subsets, defined as CD21(-)IgM(high)CD11R1(+)CD11c(+)CD14(+) and CD21(-)IgM(high) CD11R1(-)CD11c(+)CD14(-) B cells...
2017: Frontiers in Immunology
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