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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/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#2
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#3
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896229/effect-of-%C3%AE-2-adrenergic-agonists-and-antagonists-on-cytokine-release-from-human-lung-macrophages-cultured-in-vitro
#4
O Piazza, R I Staiano, E De Robertis, G Conti, V Di Crescenzo, S Loffredo, G Marone, G Zito Marinosci, M M Cataldi
The most trusted hypothesis to explain how α2-adrenergic agonists may preserve pulmonary functions in critically ill patients is that they directly act on macrophages by interfering with an autocrine/paracrine adrenergic system that controls cytokine release through locally synthetized noradrenaline and α1- and α2-adrenoreceptors. We tested this hypothesis in primary cultures of resident macrophages from human lung (HLMs). HLMs were isolated by centrifugation on percoll gradients from macroscopically healthy human lung tissue obtained from four different patients at the time of lung resection for cancer...
November 2016: Translational Medicine @ UniSa
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#5
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894870/a-benzo-b-thiophene-based-selective-type-4-s1p-receptor-agonist
#6
Wooyoung Hur, Hugh Rosen, Nathanael S Gray
S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding with S1P that have important roles in the regulation of the immune system. A potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis and several 'second generation' drugs are under clinical development. Subtype-selective agonists have been reported for each S1PR isotype, some of which are used as pharmacological tools for functional studies. Here we report the discovery and initial characterization of compound 5c, a benzo[b]thiophene amino carboxylate which exhibits potent and selective agonist activity for S1PR4...
November 18, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27892938/dendritic-cell-function-and-pathogen-specific-t-cell-immunity-are-inhibited-in-mice-administered-levonorgestrel-prior-to-intranasal-chlamydia-trachomatis-infection
#7
Nirk E Quispe Calla, Rodolfo D Vicetti Miguel, Ao Mei, Shumin Fan, Jocelyn R Gilmore, Thomas L Cherpes
The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems for long-acting reversible contraception provides strong impetus to define immunomodulatory properties of this exogenous progestin. In initial in vitro studies herein, we found LNG significantly impaired activation of human dendritic cell (DCs) and their capacity to promote allogeneic T cell proliferation. In follow-up studies in a murine model of intranasal Chlamydia trachomatis infection, we analogously found that LNG treatment prior to infection dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at 2 days post infection (dpi)...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892642/new-approaches-to-non-surgical-sterilization-for-dogs-and-cats-opportunities-and-challenges
#8
Linda Rhodes
Over the last 40 years, researchers have explored methods to non-surgically suppress fertility in animals. Immunocontraception has been used to control wildlife populations but does not confer long-term immunity. The gonadotropin-releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide 6-month to 1-year suppression of fertility in male dogs, is available commercially in some countries. Neither of these approaches provide permanent sterility. A single-dose, permanent treatment would be a valuable tool in dog and cat population control...
November 28, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27891512/a-de-o-acylated-lipooligosaccharide-based-adjuvant-system-promotes-antibody-and-th1-type-immune-responses-to-h1n1-pandemic-influenza-vaccine-in-mice
#9
Ji In Ryu, Shin Ae Park, Seo Ri Wui, Ara Ko, Ji Eun Han, Jung Ah Choi, Man Ki Song, Kwang Sung Kim, Yang Je Cho, Na Gyong Lee
Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#10
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890262/what-is-the-role-of-novel-thrombopoietic-agents-in-the-management-of-acute-leukemia
#11
REVIEW
David J Kuter
The role of novel thrombopoietic agents in the management of acute leukemia is a tale of two molecules, romiplostim and eltrombopag. Both are thrombopoietin (TPO) receptor agonists with somewhat different mechanisms of action. Romiplostim is a peptide TPO receptor agonist that activates the TPO receptor by binding to it just like TPO. Eltrombopag is a nonpeptide TPO receptor agonist that activates the TPO receptor by binding to the transmembrane domain. Both TPO receptor agonists increase platelet counts in healthy humans and in those with immune thrombocytopenia...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27885890/use-of-a-thrombopoietin-receptor-agonist-in-von-willebrand-disease-type-2b-p-v1316m-with-severe-thrombocytopenia-and-intracranial-hemorrhage
#12
O Espitia, C Ternisien, C Agard, P Boisseau, C V Denis, M Fouassier
We present here a 63-year old woman with a long history of immune thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage with thrombocytopenia. Following inefficient treatment of four platelet transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy. Her mother and sister also had chronic thrombocytopenia. Clinical history, hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type 2B with the mutation (c...
November 25, 2016: Platelets
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#13
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27881605/monocytes-and-dendritic-cells-are-the-primary-sources-of-interleukin-37-in-human-immune-cells
#14
Ina Rudloff, Steven X Cho, Jason C Lao, Devi Ngo, Matthew McKenzie, Claudia A Nold-Petry, Marcel F Nold
The interleukin (IL)-1 family member IL-37 is one of few anti-inflammatory cytokines, and it is capable of countering a broad spectrum of proinflammatory assaults. Although it is known that leukocytes are a major source of IL-37, knowledge on IL-37 production and secretion in specific immune cell types remains limited. Thus, we investigated IL-37 mRNA expression as well as protein production and secretion in human PBMCs. In PBMCs stimulated with agonists of Toll-like receptors (TLRs) 1-6 and 9, IL1F7 (the IL-37-encoding gene) was induced up to 9-fold, peaked at 6-8 h and returned to steady-state at 72 h...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27881603/a-protective-role-of-il-37-in-cancer-a-new-hope-for-cancer-patients
#15
REVIEW
Ayoub Abulkhir, Suzanne Samarani, Devendra Amre, Michel Duval, Elie Haddad, Daniel Sinnett, Jean-Marie Leclerc, Caroline Diorio, Ali Ahmad
IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27879053/n-arylsulfonyl-indolines-as-retinoic-acid-receptor-related-orphan-receptor%C3%A2-%C3%AE-ror%C3%AE-agonists
#16
Christelle Doebelin, Rémi Patouret, Ruben D Garcia-Ordonez, Mi Ra Chang, Venkatasubramanian Dharmarajan, Dana S Kuruvilla, Scott J Novick, Li Lin, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
The nuclear retinoic acid receptor-related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (TH 17) cell proliferation. As such, synthetic small-molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH 17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy...
November 23, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27876497/hepatitis-c-virus-inhibits-cd4-t-cell-function-via-binding-to-toll-like-receptor-7
#17
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/27876117/neonatal-abstinence-syndrome-and-the-gastrointestinal-tract
#18
Denise Maguire, Maureen Gröer
Development of a healthy gut microbiome is essential in newborns to establish immunity and protection from pathogens. Recent studies suggest that infants who develop dysbiosis may be at risk for lifelong adverse health consequences. Exposure to opioid drugs during pregnancy is a factor of potential importance for microbiome health that has not yet been investigated. Since these infants are born after an entire gestation exposed to mu opioid receptor agonists and have severe gastrointestinal and neurological symptoms, we hypothesize that these infants are at risk for dysbiosis...
December 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27872237/flagellin-mediated-protection-against-intestinal-yersinia-pseudotuberculosis-infection-does-not-require-interleukin-22
#19
Rémi Porte, Laurye Van Maele, Natalia Muñoz-Wolf, Benoit Foligné, Laure Dumoutier, Julien Tabareau, Delphine Cayet, Pierre Gosset, Nicolas Jonckheere, Isabelle Van Seuningen, A José Chabalgoity, Michel Simonet, Mohamed Lamkanfi, Jean-Christophe Renauld, Jean-Claude Sirard, Christophe Carnoy
Signaling through toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine)...
November 21, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27870876/reduced-picd-in-monocytes-mounts-altered-neonate-immune-response-to-candida-albicans
#20
Stephan Dreschers, Peter Saupp, Mathias Hornef, Andrea Prehn, Christopher Platen, Joachim Morschhäuser, Thorsten W Orlikowsky
BACKGROUND: Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). HYPOTHESIS: Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses...
2016: PloS One
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