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Mona S Abdellateif, Sabry M Shaarawy, Eman Z Kandeel, Ahmed H El-Habashy, Mohamed L Salem, Motawa E El-Houseini
Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through in vitro optimization of a viable DC-based vaccine. Immature DCs were primed by viable MCF-7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MHC)-II expression, in addition to different T cell subpopulations, namely CD4+ T cells, CD8+ T cells, and CD4+ CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), by flow cytometric analysis...
July 2018: Oncology Letters
Xinsheng Lin, Xiayan Zhuang, Chuangwei Li, Xin Wang
The aim of the present study was to investigate the functional status of dendritic cells (DCs) in nasal polyps (NP) and their interactions with T lymphocytes. The interactions between DC and T lymphocytes in the pathogenesis of NP was also studied. The expression of cluster of differentiation (CD)1a and CD83 in NP was detected using immunohistochemistry and the ratio of CD83 DC/CD1a+DC was counted. The distribution of DCs in NP and normal inferior turbinate mucosa (nITM) was evaluated using double immunostaining (CD1a/CD40) and low illumination fluorescence microscopy...
June 2018: Experimental and Therapeutic Medicine
Ophélie Alyssa Martin, Armand Garot, Sandrine Le Noir, Jean-Claude Aldigier, Michel Cogné, Eric Pinaud, François Boyer
In B-lineage cells, the cytidine deaminase AID not only generates somatic mutations to variable regions of Ig genes but also inflicts, at a lower frequency, mutations to several non-Ig genes named AID off-targets, which include proto-oncogenes. High-throughput sequencing should be in principle the method of choice to detect and document these rare nucleotide substitutions. So far, high-throughput sequencing-based methods are impaired by a global sequencing error rate that usually covers the real mutation rate of AID off-target genes in activated B cells...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiao-Ran Yu, Qiao-Sheng Wen, Yi Xiao, Rui Tang, Fu-Xi Li, Wen-Feng Shao, Yan-Lin Yu, Jing-Bo Xiong
OBJECTIVE: To study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation. METHODS: Human monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4, and further to mature dendritic cells using TNF-α. PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Marina Doebbeler, Christina Koenig, Lena Krzyzak, Christine Seitz, Andreas Wild, Thomas Ulas, Kevin Baßler, Dmitry Kopelyanskiy, Alina Butterhof, Christine Kuhnt, Simon Kreiser, Lena Stich, Elisabeth Zinser, Ilka Knippertz, Stefan Wirtz, Christin Riegel, Petra Hoffmann, Matthias Edinger, Lars Nitschke, Thomas Winkler, Joachim L Schultze, Alexander Steinkasserer, Matthias Lechmann
Foxp3-positive regulatory T cells (Tregs) are crucial for the maintenance of immune homeostasis and keep immune responses in check. Upon activation, Tregs are transferred into an effector state expressing transcripts essential for their suppressive activity, migration, and survival. However, it is not completely understood how different intrinsic and environmental factors control differentiation. Here, we present for the first time to our knowledge data suggesting that Treg-intrinsic expression of CD83 is essential for Treg differentiation upon activation...
June 7, 2018: JCI Insight
Markus D Lacher, Gerhard Bauer, Brian Fury, Sanne Graeve, Emily L Fledderman, Tye D Petrie, Dane P Coleal-Bergum, Tia Hackett, Nicholas H Perotti, Ying Y Kong, William W Kwok, Joseph P Wagner, Charles L Wiseman, William V Williams
Targeted cancer immunotherapy with irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic cancer cell lines has been an effective approach to reduce tumor burden in several patients. It is generally assumed that to be effective, these cell lines need to express immunogenic antigens coexpressed in patient tumor cells, and antigen-presenting cells need to take up such antigens then present them to patient T cells. We have previously reported that, in a phase I pilot study (ClinicalTrials...
2018: Frontiers in Immunology
Eleonora Turrini, Elena Catanzaro, Manuele G Muraro, Valeria Governa, Emanuele Trella, Valentina Mele, Cinzia Calcabrini, Fabiana Morroni, Giulia Sita, Patrizia Hrelia, Massimo Tacchini, Carmela Fimognari
The ability of anticancer treatments to promote the activation of tumor-reactive adaptive immune responses is emerging as a critical requirement underlying their clinical effectiveness. We investigated the ability of Hemidesmus indicus , a promising anticancer botanical drug, to stimulate immunogenic cell death in a human colorectal cancer cell line (DLD1). Here we show that Hemidesmus treatment induces tumor cell cytotoxicity characterized by surface expression of calreticulin, increased HSP70 expression and release of ATP and HMGB1...
May 11, 2018: Oncotarget
Xi Chen, Juan Bai, Xuewei Liu, Zhongbao Song, Qiaoya Zhang, Xianwei Wang, Ping Jiang
Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection. One mechanism used by viruses to evade the immune system is to cripple the antigen processing machinery in monocyte-derived dendritic cells (MoDCs). In this study, we show that MoDCs infected by PRRSV express lower levels of the MHC-peptide complex proteins TAP1 and ERp57, are impaired in their ability to stimulate T cell proliferation, and increase their production of CD83...
May 23, 2018: Journal of Virology
Rui Zhang, Qing Sun, Yi Chen, Ximeng Sun, Yuan Gu, Zhang Zhao, Yuli Cheng, Limei Zhao, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways. METHODS AND FINDINGS: After blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced...
May 18, 2018: PLoS Neglected Tropical Diseases
Sajad Karampoor, Hamid Zahednasab, Masoud Etemadifar, Hossein Keyvani
Multiple Sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS) in which immune system plays a crucial role in progression of the disease. An enormous amount of research has been shown that immune mediators such as cytokines and chemokines are the culprits of MS propagation suggesting that modulation of such molecules may pave the path to hinder the disease development. It has been shown that both CD21 and CD83 contribute to the resolution of inflammation occurred in MS. CD21 and CD83 have also been ascribed to Epstein Barr virus (EBV) infection (the prime suspect of MS causality) and the levels of vitamin D, respectively...
July 15, 2018: Journal of Neuroimmunology
Yue He, Chaokui Wang, Guannan Su, Bolin Deng, Zi Ye, Yang Huang, Gangxiang Yuan, Kijlstra Aize, Hong Li, Peizeng Yang
PURPOSE: A20 is a ubiquitously expressed and inducible cytosolic protein, which plays an important role in the negative regulation of inflammation and immunity. In this study, we investigated the role of A20 in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease. METHODS: The levels of A20 in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were detected in BD patients with active and inactive uveitis, VKH patients with active and inactive uveitis, and normal subjects, respectively, by real-time PCR...
April 26, 2018: British Journal of Ophthalmology
Pavla Taborska, Jirina Bartunkova, Daniel Smrz
Dendritic cells (DCs) and mast cells (MCs) are key players of the immune system, often coming in close proximity in peripheral tissues. The interplay of these cells is, however, still poorly understood, especially with regards to human cells. The reason for that is the absence of a well established in vitro human cell-based study system that would allow a simultaneous preparation of both cell types. In this study, we show a method for simultaneous generation of DCs and MCs from CD34+ stem cell progenitors that were isolated from the non-adherent fraction of non-mobilized peripheral blood mononuclear cells of healthy donors...
July 2018: Journal of Immunological Methods
Naveen Surendran, Andrea Simmons, Michael E Pichichero
Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants...
May 2018: Innate Immunity
Kuan Y Wong, Rebecca Baron, Therese A Seldon, Martina L Jones, Alison M Rice, David J Munster
Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83+ human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
A Liu, J Frostegård
BACKGROUND: Activated T cells and dendritic cells (DCs) occur in atherosclerotic plaques. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the LDL-receptor (LDLR) and results in increased LDL levels. We here investigate immune effects of PCSK9 on OxLDL induced DC maturation and T-cell activation. METHODS: T cells were isolated from carotid specimens of patients undergoing carotid endarterectomy or from peripheral blood of healthy individuals. Human peripheral blood monocytes were differentiated into DCs...
April 4, 2018: Journal of Internal Medicine
Felipe Melo-Gonzalez, Thomas M Fenton, Cecilia Forss, Catherine Smedley, Anu Goenka, Andrew S MacDonald, David J Thornton, Mark A Travis
Cross-talk between different components of the intestinal barrier and the immune system may be important in maintaining gut homeostasis. A crucial part of the gut barrier is the mucus layer, a cross-linked gel on top of the intestinal epithelium that consists predominantly of the mucin glycoprotein MUC2. However, whether the mucin layer actively regulates intestinal immune cell responses is not clear. As recent evidence suggests that intestinal dendritic cells (DCs) may be regulated by the mucus layer, we purified intestinal mucin, incubated with human DCs and determined functional effects...
March 26, 2018: Journal of Biological Chemistry
Ralf Küppers
No abstract text is available yet for this article.
April 2018: Haematologica
Xi Chen, Shengnan Hao, Zhonghua Zhao, Jia Liu, Qianqian Shao, Fang Wang, Dong Sun, Ying He, Wenjuan Gao, Haiting Mao
IL-35, a novel IL-12 family member, is a potent inhibitory cytokine predominantly produced by regulatory T and B lymphocytes that exerts optimal suppression in immune response. However, it remains unclear whether IL-35 plays an inhibitory role on human dendritic cells. In the present study, we focused on the possible immunosuppressive effect of IL-35 on the differentiation, maturation and function of monocyte-derived DCs (MoDCs). Addition of exogenous IL-35 was able to partially suppress MoDCs differentiation in vitro...
August 2018: Cytokine
C Napoletano, S Mattiucci, A Colantoni, F Battisti, I G Zizzari, H Rahimi, M Nuti, A Rughetti
Human dendritic cells (DCs) show remarkable phenotypic changes when matured in the presence of helminth-derived products. These modifications frequently elicited a polarization towards Th2 cells and regulatory T cells thus contributing to immunological tolerance against these pathogens. In this study, the interaction between DCs and larvae of the zoonotic anisakid nematode Anisakis pegreffii was investigated. A. pegreffii larvae were collected from fish hosts, and monocyte-derived DCs were cocultured in the presence of the live larvae (L) or its crude extracts (CE)...
May 2018: Parasite Immunology
Katrina K Ki, Helen M Faddy, Robert L Flower, Melinda M Dean
Transfusion of packed red blood cells (PRBCs) modulates patients' immune responses and clinical outcomes; however, the underpinning mechanism(s) remain unknown. The potential for PRBC to modulate myeloid dendritic cells (mDC) and blood DC antigen 3 was assessed using an in vitro transfusion model. In parallel, to model processes activated by viral or bacterial infection, toll-like receptor agonists polyinosinic:polycytidylic acid or lipopolysaccharide were added. Exposure to PRBC upregulated expression of CD83 and downregulated CD40 and CD80 on both DC subsets, and it suppressed production of interleukin (IL)-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-gamma-inducible protein-10 by these cells...
March 2018: Journal of Interferon & Cytokine Research
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