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Immune exosome

Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
Nilubon Singhto, Rattiyaporn Kanlaya, Angkhana Nilnumkhum, Visith Thongboonkerd
In kidney stone disease, macrophages secrete various mediators via classical secretory pathway and cause renal interstitial inflammation. However, whether their extracellular vesicles, particularly exosomes, are involved in kidney stone pathogenesis remained unknown. This study investigated alterations in exosomal proteome of U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) after exposure to calcium oxalate monohydrate (COM) crystals for 16-h using 2-DE-based proteomics approach. Six significantly altered proteins in COM-treated exosomes were successfully identified by nanoscale liquid chromatography-electrospray ionization-electron transfer dissociation tandem mass spectrometry as proteins involved mainly in immune processes, including T-cell activation and homeostasis, Fcγ receptor-mediated phagocytosis, interferon-γ (IFN-γ) regulation, and cell migration/movement...
2018: Frontiers in Immunology
Oliver Grünvogel, Ombretta Colasanti, Ji-Young Lee, Volker Klöss, Sandrine Belouzard, Anna Reustle, Katharina Esser-Nobis, Jasper Hesebeck-Brinckmann, Pascal Mutz, Katrin Hoffmann, Arianeb Mehrabi, Ronald Koschny, Florian W R Vondran, Daniel Gotthardt, Paul Schnitzler, Christoph Neumann-Haefelin, Robert Thimme, Marco Binder, Ralf Bartenschlager, Jean Dubuisson, Alexander H Dalpke, Volker Lohmann
BACKGROUND & AIMS: Hepatitis C virus (HCV) infections most often result in chronic outcomes, although the virus constantly produces replication intermediates, in particular double-stranded RNA (dsRNA), representing potent inducers of innate immunity. We aimed to characterize the fate of HCV dsRNA in hepatocyte cultures to identify mechanisms contributing to viral persistence in presence of an active innate immune response. METHODS: We analyzed hepatocyte-based culture models for HCV for induction of innate immunity, secretion of virus positive- or negative-strand RNA, and viral replication using different quantification methods and microscopy techniques...
March 10, 2018: Gastroenterology
Jing Ni, Yuxi Sun, Zheng Liu
In recent years, the cardiac protective mechanisms of stem cells have become a research focus. Increasing evidence has suggested that stem cells release vesicles, including exosomes and micro-vesicles. The content of these vesicles relies on an extracellular stimulus, and active ingredients are extensively being studied. Previous studies have confirmed that stem cell-derived exosomes have a cardiac protective function similar to that of stem cells, and promote angiogenesis, decrease apoptosis, and respond to stress...
March 10, 2018: Journal of Cardiovascular Translational Research
Yong-Seok Kim, Jae-Sung Ahn, Semi Kim, Hyun-Jin Kim, Shin-Hee Kim, Ju-Seop Kang
Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells...
March 2018: Korean Journal of Physiology & Pharmacology
Lin Zhang, Changfu Hao, Sanqiao Yao, Rong Tang, Wei Guo, Hongbin Cong, Jiangfeng Li, Lei Bao, Di Wang, Yiping Li, Xinghao Yu, Shuyin Duan, Wu Yao
Inhaling a dangerous amount of nanoparticles leads to pulmonary inflammatory and immune disorders, which integrates several kinds of cells. Exosomes are suggested to play a crucial role in intercellular communication via miRNA transmission. To investigate the role of exosomal miRNA in nanoparticle phagocytosis, a total of 54 pneumoconiosis patients along with 100 healthy controls are recruited, exosomes derived from their venous blood are collected, and then exosomal miRNAs are profiled with high-throughput sequencing technology...
March 8, 2018: Small
Le Guo, Xi-Qiu Xu, Li Zhou, Run-Hong Zhou, Xu Wang, Jie-Liang Li, Jin-Biao Liu, Hang Liu, Biao Zhang, Wen-Zhe Ho
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5...
2018: Frontiers in Immunology
Priyanka Sharma, Sonja Ludwig, Laurent Muller, Chang Sook Hong, John M Kirkwood, Soldano Ferrone, Theresa L Whiteside
Tumour-derived exosomes (TEX) are a subset of extracellular vesicles (EVs) present in body fluids of patients with cancer. The role of this exosome subset in melanoma progression has been of interest ever since ex vivo studies of exosomes produced by melanoma cell lines were shown to suppress anti-melanoma immune responses. To study the impact of melanoma-derived exosomes (MTEX) present in patients' plasma on melanoma progression, isolation of MTEX from total plasma exosomes is necessary. We have developed an immunoaffinity-based method for MTEX capture from plasma of melanoma patients...
2018: Journal of Extracellular Vesicles
Yuting Liang, Longwei Qiao, Xia Peng, Zelin Cui, Yue Yin, Huanjin Liao, Min Jiang, Li Li
Mast cells are important effector cells of the immune system, and mast cell-derived exosomes carrying RNAs play a role in immune regulation. However, the molecular function of mast cell-derived exosomes is currently unknown, and here, we identify differentially expressed genes (DEGs) in mast cells and exosomes. We isolated mast cells derived exosomes through differential centrifugation and screened the DEGs from mast cell-derived exosomes, using the GSE25330 array dataset downloaded from the Gene Expression Omnibus database...
2018: American Journal of Translational Research
Bengang Xing, Xiangzhao Ai, Ming Hu, Zhimin Wang, Wenmin Zhang, Juan Li, Jun Lin, Huang-Hao Yang
In terms of the extremely small size and large specific surface area, nanomaterials often exhibit unusual physical and chemical properties, which have recently attracted considerable attention in bionanotechnology and nanomedicine. Currently, the extensive usage of nanotechnology in medicine holds the great potential for precise diagnosis and effective therapeutics of various human diseases in clinical practice in past decades. However, a detailed understanding regarding how nanomedicines interact with the intricate environment in complex living systems remains a pressing and challenging goal...
March 6, 2018: Bioconjugate Chemistry
Antonio Garcia-Gomez, Javier Rodríguez-Ubreva, Esteban Ballestar
Compelling evidences highlight the critical role of the tumor microenvironment as mediator of tumor progression and immunosuppression in several types of cancer. The reciprocal interplay between neoplastic and non-tumoral host cells is mediated by direct cell-to-cell contact, soluble factors and exosomes that result in differential gene expression patterns that are driven by epigenetic mechanisms. In this regard, extensive literature has described the abnormalities in the DNA methylation status and histone modification profiles in tumor cells...
February 28, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Poornima Venkat, Michael Chopp, Jieli Chen
Stroke is a global health concern and it is imperative that therapeutic strategies with wide treatment time frames be developed to improve neurological outcome in patients. Patients with diabetes mellitus who suffer a stroke have worse neurological outcomes and long-term functional recovery than nondiabetic stroke patients. Diabetes induced vascular damage and enhanced inflammatory milieu likely contributes to worse post stroke outcomes. Diabetic stroke patients have an aggravated pathological cascade, and treatments that benefit nondiabetic stroke patients do not necessarily translate to diabetic stroke patients...
March 2, 2018: Stem Cells Translational Medicine
Muthukumar Gunasekaran, Monal Sharma, Ramsey Hachem, Ross Bremner, Michael A Smith, Thalachallour Mohanakumar
Circulating exosomes containing donor HLA and lung-associated self-antigens (SAg) are thought to play an important role in allograft rejection after human lung transplantation. We characterized exosomes isolated from serum of 10 lung transplant recipients (LTxR) diagnosed with bronchiolitis obliterans syndrome (BOS) and compared them with exosomes isolated from serum of 10 stable LTxR. Lung-associated SAg (K-α-1-tubulin [Kα1T] and collagen V [Col-V]), MHC class II molecules, costimulatory molecules CD40, CD80, and CD86, and transcription factors class II MHC trans -activator, NF-κB, hypoxia-inducible factor 1-α, IL-1R-associated kinase 1, MyD88, and 20S proteasome were detected in exosomes from BOS, but not stable LTxR...
February 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Mads Eggert Nielsen, Hans Thordal-Christensen
Plant innate immunity enables plants to defend themselves against infectious pathogens. While membrane trafficking and release of exosomes are considered vital for correct execution of innate immunity, the mechanisms behind remain elusive. Recently, we have shown that VPS9a, the general guanine-nucleotide exchange factor activating Rab5 GTPases, is required for both pre- and post-invasive immunity against powdery mildew fungi in Arabidopsis thaliana. Yet, the Arabidopsis genome contains a close homologue of VPS9a, which potentially plays specific roles in innate immunity...
February 27, 2018: Plant Signaling & Behavior
Wenchao Zhang, Xiaofeng Jiang, Jinghui Bao, Yi Wang, Huixing Liu, Lijun Tang
Exosomes are extracellular vesicles derived from cell endocytosis which act as transmitters between cells. They are composed of proteins, lipids, and RNAs through which they participate in cellular crosstalk. Consequently, they play an important role in health and disease. Our view is that exosomes exert a bidirectional regulatory effect on pathogen infections by delivering their content. First, exosomes containing proteins and RNAs derived from pathogens can promote infections in three ways: (1) mediating further infection by transmitting pathogen-related molecules; (2) participating in the immune escape of pathogens; and (3) inhibiting immune responses by favoring immune cell apoptosis...
2018: Frontiers in Immunology
Fruzsina Hobor, Andre Dallmann, Neil J Ball, Carla Cicchini, Cecilia Battistelli, Roksana W Ogrodowicz, Evangelos Christodoulou, Stephen R Martin, Alfredo Castello, Marco Tripodi, Ian A Taylor, Andres Ramos
Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition)...
February 26, 2018: Nature Communications
Danyue Peng, Huifang Wang, Lei Li, Xiao Ma, Ying Chen, Hao Zhou, Yi Luo, Yin Xiao, Lingbo Liu
Leukemia stem cells (LSCs) are responsible for acute myeloid leukemia (AML) chemotherapy resistance and relapse. Here, we discovered that miR-34c-5p, a microRNA central to the senescence regulation network, was significantly down-regulated in AML (non-acute promyelocytic leukemia, non-APL) stem cells compared to that in normal hematopoietic stem cells (HSCs). The lower expression of miR-34c-5p in LSCs was closely correlated to the adverse prognosis and poor responses to therapy of AML patients. Increased miR-34c-5p expression induced LSCs senescence ex vivo, prevented leukemia development and promoted the eradication of LSCs in immune deficient mice...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
John Eppensteiner, Robert Patrick Davis, Andrew S Barbas, Jean Kwun, Jaewoo Lee
Despite significant improvements in injury prevention and emergency response, injury-related death and morbidity continues to increase in the US and worldwide. Patients with trauma, invasive operations, anti-cancer treatment, and organ transplantation produce a host of danger signals and high levels of pro-inflammatory and pro-thrombotic mediators, such as damage-associated molecular patterns (DAMPs) and extracellular vesicles (EVs). DAMPs (e.g., nucleic acids, histone, high-mobility group box 1 protein, and S100) are molecules released from injured, stressed, or activated cells that act as endogenous ligands of innate immune receptors, whereas EVs (e...
2018: Frontiers in Immunology
Tomer Cooks, Ioannis S Pateras, Lisa M Jenkins, Keval M Patel, Ana I Robles, James Morris, Tim Forshew, Ettore Appella, Vassilis G Gorgoulis, Curtis C Harris
TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes...
February 22, 2018: Nature Communications
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