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Immunological pathways

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https://www.readbyqxmd.com/read/29777224/progression-of-whole-blood-transcriptional-signatures-from-interferon-induced-to-neutrophil-associated-patterns-in-severe-influenza
#1
Jake Dunning, Simon Blankley, Long T Hoang, Mike Cox, Christine M Graham, Philip L James, Chloe I Bloom, Damien Chaussabel, Jacques Banchereau, Stephen J Brett, Miriam F Moffatt, Anne O'Garra, Peter J M Openshaw
Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29775752/the-genetics-and-molecular-pathogenesis-of-systemic-lupus-erythematosus-sle-in-populations-of-different-ancestry
#2
REVIEW
George N Goulielmos, Maria I Zervou, Vassilis M Vazgiourakis, Yogita Ghodke-Puranik, Alexandros Garyfallos, Timothy B Niewold
Systemic lupus erythematosus (SLE; OMIM 152700) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and a multi-system involvement commonly affecting the skin, renal, musculoskeletal, and hematopoetic systems clinical manifestations involving. Disease features range from mild manifestations, such as rash or arthritis, to life-threatening end-organ manifestations, such as glomerulonephritis or thrombosis, and it is difficult to predict which manifestations will affect a given patient...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29772561/thyroid-cancer-phenotypes-in-relation-to-inflammation-and-autoimmunity
#3
Loredana Pagano, Chiara Mele, Maria Teresa Sama, Marco Zavattaro, Marina Caputo, Lucrezia De Marchi, Samuele Paggi, Flavia Prodam, Gianluca Aimaretti, Paolo Marzullo
Thyroid cancer represents the most frequent endocrine neoplasm and is epidemiologically linked to a growing incidence worldwide, which is only in part explained by the increased detection of small cancers in a preclinical stage. Understanding the molecular pathogenesis of well-differentiated thyroid cancers and poorly-differentiated thyroid cancers has prompted interest into the identification of crucial signaling pathways and molecular derangements related to genetic and epigenetic alterations. Increasing attention has been recently focused on inflammation and immunity as major culprit mechanisms involved in thyroid tumourigenesis, through the detection of activated immune cells, pro-inflammatory cytokines, as well as signal integrations between inflammatory and proliferative pathways within the thyroid tumour micro-environment...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29769578/metabolomic-profile-of-systemic-sclerosis-patients
#4
Federica Murgia, Silvia Svegliati, Simone Poddighe, Milena Lussu, Aldo Manzin, Tatiana Spadoni, Colomba Fischetti, Armando Gabrielli, Luigi Atzori
Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1 H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#5
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768175/targeting-the-latent-reservoir-for-hiv-1
#6
REVIEW
Srona Sengupta, Robert F Siliciano
Antiretroviral therapy can effectively block HIV-1 replication and prevent or reverse immunodeficiency in HIV-1-infected individuals. However, viral replication resumes within weeks of treatment interruption. The major barrier to a cure is a small pool of resting memory CD4+ T cells that harbor latent HIV-1 proviruses. This latent reservoir is now the focus of an intense international research effort. We describe how the reservoir is established, challenges involved in eliminating it, and pharmacologic and immunologic strategies for targeting this reservoir...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29766256/monogenic-systemic-lupus-erythematosus-insights-in-pathophysiology
#7
REVIEW
Ezgi Deniz Batu
Systemic lupus erythematosus (SLE) is a complex disease with different genetic, immunologic, and environmental factors contributing to the pathogenesis. Monogenic SLE could help us understand the main phases of immune dysregulation in SLE. The aim of this review is to summarize the current knowledge on monogenic SLE with the implications of the respective genes on disease pathogenesis. A comprehensive literature search on monogenic SLE was conducted utilizing the Cochrane Library and MEDLINE/PubMed databases...
May 15, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#8
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29761483/epithelial-barrier-dysfunctions-in-atopic-dermatitis-a-skin-gut-lung-model-linking-microbiome-alteration-and-immune-dysregulation
#9
REVIEW
T H Zhu, T R Zhu, K A Tran, R K Sivamani, V Y Shi
Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces TH 2 inflammatory response and a thymic stromal lymphopoietin mediated pathway that further promotes barrier breakdown at distant sites including the intestinal and respiratory tract. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march...
May 15, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29760736/comparison-of-immunological-characteristics-of-mesenchymal-stem-cells-from-the-periodontal-ligament-umbilical-cord-and-adipose-tissue
#10
Jin-Hee Kim, Chris H Jo, Hang-Rae Kim, Young-Il Hwang
Mesenchymal stem cells (MSCs) are of therapeutic importance in the fields of regenerative medicine and immunological diseases. Accordingly, studies evaluating MSCs for clinical applications are increasing. In this study, we characterized MSCs from the periodontal ligament, umbilical cord (UC-MSCs), and adipose tissue, which were relatively easy to obtain with limited ethical concerns regarding their acquisition, and compared their immunological characteristics. Among MSCs isolated from the three different tissues, UC-MSCs grew the fastest in vitro ...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760711/selective-modulation-of-tnf-tnfrs-signaling-insights-for-multiple-sclerosis-treatment
#11
REVIEW
Valentina Pegoretti, Wia Baron, Jon D Laman, Ulrich L M Eisel
Autoimmunity develops when self-tolerance mechanisms are failing to protect healthy tissue. A sustained reaction to self is generated, which includes the generation of effector cells and molecules that destroy tissues. A way to restore this intrinsic tolerance is through immune modulation that aims at refurbishing this immunologically naïve or unresponsive state, thereby decreasing the aberrant immune reaction taking place. One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNFα) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29757266/spatial-and-temporal-control-of-t-cell-activation-using-a-photoactivatable-agonist
#12
Elisa Sanchez, Morgan Huse
T lymphocytes engage in rapid, polarized signaling, occurring within minutes following TCR activation. This induces formation of the immunological synapse, a stereotyped cell-cell junction that regulates T cell activation and directionally targets effector responses. To study these processes effectively, an imaging approach that is tailored to capturing fast, polarized responses is necessary. This protocol describes such a system, which is based on a photoactivatable peptide-major histocompatibility complex (pMHC) that is non-stimulatory until it is exposed to ultraviolet light...
April 25, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29753885/immunological-responses-to-influenza-vaccination-lessons-for-improving-vaccine-efficacy
#13
REVIEW
Taia T Wang, Stylianos Bournazos, Jeffrey V Ravetch
A critical factor in the maturation of influenza vaccine responses is the nearly inevitable binding of vaccine antigens by exiting anti-influenza IgGs. These antigen-IgG immune complexes direct the response to immunization by modulating cellular processes that determine antibody and T-cell repertoires: maturation of dendritic cells, processing and presentation of antigens to T cells, trafficking of antigens to the germinal center, and selection of B cells for antibody production. By focusing on the recent advances in the study of the immunomodulatory processes mediated by IgG immune complexes upon influenza vaccination, we discuss a pathway that is critical for modulating the breadth and potency of anti-HA antibody responses and has previously led to the development of strategies to improve influenza vaccine efficacy...
May 10, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29750504/c1q-mediated-complement-activation-and-c3-opsonization-trigger-recognition-of-stealth-poly-2-methyl-2-oxazoline-coated-silica-nanoparticles-by-human-phagocytes
#14
Regina Tavano, Luca Gabrielli, Elisa Lubian, Chiara Fedeli, Silvia Visentin, Patrizia Polverino de Laureto, Giorgio Arrigoni, Alessandra Geffner-Smith, Fangfang Chen, Dmitri Simberg, Giulia Morgese, Edmondo Maria Benetti, Linping Wu, Seyed Moein Moghimi, Fabrizio Mancin, Emanuele Papini
Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol), (PEG), for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA engineered NPs have shown comparable pharmacokinetics, and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyl-triethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes and macrophages, and compared their performance with PEGylated and uncoated NP counterparts...
May 11, 2018: ACS Nano
https://www.readbyqxmd.com/read/29749649/transgelin-2-in-immunity-its-implication-in-cell-therapy
#15
REVIEW
Suin Jo, Hye-Ran Kim, YeVin Mun, Chang-Duk Jun
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages...
May 11, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29741731/expression-of-grim-19-in-unexplained-recurrent-spontaneous-abortion-and-possible-pathogenesis
#16
Yang Yang, Laiyang Cheng, Xiaohui Deng, Hongling Yu, Lan Chao
STUDY QUESTION: Is aberrant expression of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) associated with unexplained recurrent spontaneous abortion (URSA)? SUMMARY ANSWER: GRIM-19 deficiency may regulate regulatory T cell/ T helper 17 cell (Treg/Th17) balance partly through reactive oxygen species (ROS) - mammalian target of rapamycin (mTOR) signaling axis in URSA. WHAT IS KNOWN ALREADY: Immunological disorders may cause impaired maternal immune tolerance to the fetus and result in fetal rejection...
May 8, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29740436/understanding-the-cellular-origin-of-the-mononuclear-phagocyte-system-sheds-light-on-the-myeloid-postulate-of-immune-paralysis-in-sepsis
#17
REVIEW
Lionel Franz Poulin, Corentin Lasseaux, Mathias Chamaillard
Sepsis, in essence, is a serious clinical condition that can subsequently result in death as a consequence of a systemic inflammatory response syndrome including febrile leukopenia, hypotension, and multiple organ failures. To date, such life-threatening organ dysfunction remains one of the leading causes of death in intensive care units, with an increasing incidence rate worldwide and particularly within the rapidly growing senior population. While most of the clinical trials are aimed at dampening the overwhelming immune response to infection that spreads through the bloodstream, based on several human immunological investigations, it is now widely accepted that susceptibility to nosocomial infections and long-term sepsis mortality involves an immunosuppressive phase that is characterized by a decrease in some subsets of dendritic cells (DCs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29736147/recombinant-interferon-alpha-2b-in-rheumatoid-arthritis-good-antigen-for-rheumatoid-arthritis-antibodies
#18
Wahid Ali Khan
Aim of the study: Interferon alpha-induced arthritis and activation of the type 1 interferon pathway during rheumatoid arthritis (RA) has been well documented but the underlying mechanism remains unclear. This study addressed the binding specificity of antibodies with recombinant interferon alpha 2b (rIFN α -2b) in sera from different RA patients. Utilization of anti-hrIFN α -2b antibodies as a probe for estimation of interferon α -2b concentration in RA patients' synovial fluid (SF) was also investigated...
2018: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/29735884/polysaccharides-extracted-from-rhizoma-pleionis-have-antitumor-properties-in-vitro-and-in-an-h22-mouse-hepatoma-ascites-model-in-vivo
#19
Yukun Fang, Anhong Ning, Sha Li, Shaozheng Zhou, Lei Liu, Thomson Patrick Joseph, Mintao Zhong, Jilong Jiao, Wei Zhang, Yonghui Shi, Meishan Zhang, Min Huang
Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP) on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29731749/adaptive-nkg2c-cd57-natural-killer-cell-and-tim-3-expression-during-viral-infections
#20
Hassen Kared, Serena Martelli, Shu Wen Tan, Yannick Simoni, Meng Li Chong, Siew Hwei Yap, Evan W Newell, Sylvia L F Pender, Adeeba Kamarulzaman, Reena Rajasuriar, Anis Larbi
Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection...
2018: Frontiers in Immunology
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