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Immune system modeling

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https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-co-inhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-of-systemic-sclerosis-patients
#1
Michelle Fleury, Anna C Belkina, Elizabeth A Proctor, Christopher Zammitti, Robert W Simms, Douglas A Lauffenburger, Jennifer E Snyder-Cappione, Robert Lafyatis, Hans Dooms
OBJECTIVE: Immune dysfunction is an important component of the disease process underlying Systemic Sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. Here, we measured the expression and function of the co-inhibitory receptors (co-IRs) PD-1, TIGIT, TIM-3, and LAG-3 in lymphocyte subsets from the peripheral blood of SSc patients. METHODS: Co-IR expression levels on immune cell subsets were analyzed using a 16-color flow cytometry panel...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29244745/immunotherapeutic-potential-of-oncolytic-h-1-parvovirus-hints-of-glioblastoma-microenvironment-conversion-towards-immunogenicity
#2
Assia L Angelova, Milena Barf, Karsten Geletneky, Andreas Unterberg, Jean Rommelaere
Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients...
December 15, 2017: Viruses
https://www.readbyqxmd.com/read/29244717/femtograms-of-interferon-%C3%AE-suffice-to-modulate-the-behavior-of-jurkat-cells-a-new-light-in-immunomodulation
#3
Sara Castiglioni, Vincenzo Miranda, Alessandra Cazzaniga, Marilena Campanella, Michele Nichelatti, Marco Andena, Jeanette A M Maier
Since interferon-γ (IFN-γ) tunes both innate and adaptive immune systems, it was expected to enter clinical practice as an immunomodulatory drug. However, the use of IFN-γ has been limited by its dose-dependent side effects. Low-dose medicine, which is emerging as a novel strategy to treat diseases, might circumvent this restriction. Several clinical studies have proved the efficacy of therapies with a low dose of cytokines subjected to kinetic activation, while no in vitro data are available. To fill this gap, we investigated whether low concentrations, in the femtogram range, of kinetically activated IFN-γ modulate the behavior of Jurkat cells, a widely used experimental model that has importantly contributed to the present knowledge about T cell signaling...
December 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29243495/the-recombinant-fusion-protein-cfp10-esat6-difn-has-protective-effect-against-tuberculosis-in-guinea-pigs
#4
Natalya V Permyakova, Pavel A Belavin, Dariya S Pirozhkova, Elena G Ufimtseva, Sergey M Rozov, Sergey R Mursalimov, Yuriy V Sidorchuk, Elena A Uvarova, Alla A Zagorskaya, Tatiana V Marenkova, Svetlana V Bannikova, Evgeniy A Demidov, Konstantin V Starostin, Marionella A Kravchenko, Diana V Vakhrusheva, Roman B Berdnikov, Natalya I Eremeeva, Sergey N Skornyakov, Sergey E Peltek, Elena V Deineko
Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response...
December 15, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29243000/rna-interference-based-therapy-and-its-delivery-systems
#5
Xiuhui Chen, Lingegowda S Mangala, Cristian Rodriguez-Aguayo, Xianchao Kong, Gabriel Lopez-Berestein, Anil K Sood
RNA interference (RNAi) is considered a highly specific approach for gene silencing and holds tremendous potential for treatment of various pathologic conditions such as cardiovascular diseases, viral infections, and cancer. Although gene silencing approaches such as RNAi are widely used in preclinical models, the clinical application of RNAi is challenging primarily because of the difficulty in achieving successful systemic delivery. Effective delivery systems are essential to enable the full therapeutic potential of RNAi...
December 14, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29242629/immune-microenvironment-of-experimental-rat-c6-gliomas-resembles-human-glioblastomas
#6
Anna Gieryng, Dominika Pszczolkowska, Katarzyna Bocian, Michal Dabrowski, Wenson David Rajan, Michal Kloss, Jakub Mieczkowski, Bozena Kaminska
Glioblastoma (GBM) is the most aggressive primary brain tumor, with ineffective anti-tumor responses and a poor prognosis despite aggressive treatments. GBM immune microenvironment is heterogenous  and activation of specific immune populations in GBM is not fully characterized. Reliable animal models are critical for defining mechanisms of anti-tumor immunity. First we analyzed the immune subpopulations present in rat C6 gliomas. Using flow cytometry we determined kinetics of infiltration of myeloid cells and T lymphocytes into glioma-bearing brains...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29242512/synthetic-integrin-binding-immune-stimulators-target-cancer-cells-and-prevent-tumor-formation
#7
Manuel Brehs, André J G Pötgens, Julia Steitz, Karine Thewes, Janett Schwarz, Anne C Conibear, Matthias Bartneck, Frank Tacke, Christian F W Becker
Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity. Here we describe the design of immune system engagers (ISErs), a novel class of synthetic peptide-based compounds that bind specifically to cancer cells and stimulate the immune system...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29242228/bmscs-ameliorate-septic-coagulopathy-through-suppressing-inflammation-in-cecal-ligation-and-puncture-induced-sepsis
#8
Shunyao Xu, Zhen Zhou, Hao Li, Ziying Liu, Xiaojun Pan, Fen Wang, Yueyue Huang, Xiaogang Li, Yunbei Xiao, Jingye Pan, Cong Wang, Dequan Li
Sepsis is an aggressive and life-threatening systemic inflammatory response with a high mortality. Inflammation and coagulation play crucial roles in the pathogenesis of sepsis in a mutually promoting manner. Unlike other single-target molecular therapies that have no obvious effects on clinical sepsis, the bone marrow stromal cell (BMSC) therapy offers a broader spectrum of activities ranging from immune and inflammation suppression to tissue regeneration. In this report, we demonstrated that BMSC injection attenuated the septic coagulopathy...
December 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29242144/recent-advances-in-understanding-the-roles-of-blood-platelets-in-the-pathogenesis-of-allergic-inflammation-and-bronchial-asthma
#9
REVIEW
Tomohiro Takeda, Hideaki Morita, Hirohisa Saito, Kenji Matsumoto, Akio Matsuda
Platelets play an essential role in hemostasis to minimize blood loss due to traumatic injury. In addition, they contain various immune-associated molecules and contribute to immunological barrier formation at sites of vascular injury, thereby protecting against invading pathogens. Platelets are also crucially involved in development of allergic diseases, including bronchial asthma. Platelets in asthmatics are more activated than those in healthy individuals. By using a murine asthma model, platelets were shown to be actively involved in progression of the disease, including in airway eosinophilia and airway remodeling...
December 11, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/29241953/innate-immune-responses-in-the-chinese-oak-silkworm-antheraea-pernyi
#10
Xialu Wang, Haoluo, Rong Zhang
Innate immunity, the evolutionarily conserved defense system, has been extensively analyzed in insect models over recent decades. The significant progress in this area has formed our dominant conceptual framework of the innate immune system, but critical advances in other insects have had a profound impact on our insights into the mystery of innate immunity. In recent years, we focused on the immune responses in Antheraea pernyi, an important commercial silkworm species reared in China. Here, we review the immune responses of A...
December 11, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29241666/identification-of-human-circadian-genes-based-on-time-course-gene-expression-profiles-by-using-a-deep-learning-method
#11
Peng Cui, Tingyan Zhong, Zhuo Wang, Tao Wang, Hongyu Zhao, Chenglin Liu, Hui Lu
Circadian genes express periodically in an approximate 24-h period and the identification and study of these genes can provide deep understanding of the circadian control which plays significant roles in human health. Although many circadian gene identification algorithms have been developed, large numbers of false positives and low coverage are still major problems in this field. In this study we constructed a novel computational framework for circadian gene identification using deep neural networks (DNN) a deep learning algorithm which can represent the raw form of data patterns without imposing assumptions on the expression distribution...
December 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29241548/diverging-mrna-and-protein-networks-in-activated-microglia-reveal-srsf3-suppresses-translation-of-highly-upregulated-innate-immune-transcripts
#12
Hejer Boutej, Reza Rahimian, Sai Sampath Thammisetty, Louis-Charles Béland, Mélanie Lalancette-Hébert, Jasna Kriz
Uncontrolled microglial activation may lead to the development of inflammation-induced brain damage. Here, we uncover a ribosome-based mechanism/checkpoint involved in control of the innate immune response and microglial activation. Using an in vivo model system for analysis of the dynamic translational state of microglial ribosomes, with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly upregulated and ribosome-associated mRNAs were not translated, resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA signature and an immunomodulatory/homeostatic protein signature...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241222/flavopiridol-enhances-abt-199-sensitivity-in-unfavourable-risk-multiple-myeloma-cells-in-vitro-and-in-vivo
#13
Liang Zhou, Yu Zhang, Deepak Sampath, Joel Leverson, Yun Dai, Maciej Kmieciak, Matthew Nguyen, Robert Z Orlowski, Steven Grant
BACKGROUND: The BCL-2-specific BH3-mimetic ABT-199 (venetoclax) has been reported to be principally active against favourable-risk multiple myeloma (MM) cells, prompting efforts to extend its activity to include more resistant, higher-risk MM subsets. METHODS: Effects of the CDK9 inhibitor flavopiridol (FP; alvocidib) on responses to ABT-199 were examined in MM cells. Cell death and protein expression were evaluated by western blot and immunofluorescence. Xenograft models were used to study combination effects in vivo...
December 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29239915/preclinical-assessment-of-car-t-cell-therapy-targeting-the-tumor-antigen-5t4-in-ovarian-cancer
#14
Gemma L Owens, Victoria E Sheard, Milena Kalaitsidou, Daniel Blount, Yatish Lad, Eleanor J Cheadle, Richard J Edmondson, Gurdeep Kooner, David E Gilham, Richard Harrop
Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer...
December 12, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29238325/probiotic-bacteria-alter-pattern-recognition-receptor-expression-and-cytokine-profile-in-a-human-macrophage-model-challenged-with-candida-albicans-and-lipopolysaccharide
#15
Victor H Matsubara, Karin H Ishikawa, Ellen S Ando-Suguimoto, Bruno Bueno-Silva, Atlas E M Nakamae, Marcia P A Mayer
Probiotics are live microorganisms that confer benefits to the host health. The infection rate of potentially pathogenic organisms such as Candida albicans, the most common agent associated with mucosal candidiasis, can be reduced by probiotics. However, the mechanisms by which the probiotics interfere with the immune system are largely unknown. We evaluated the effect of probiotic bacteria on C. albicans challenged human macrophages. Macrophages were pretreated with lactobacilli alone (Lactobacillus rhamnosus LR32, Lactobacillus casei L324m, or Lactobacillus acidophilus NCFM) or associated with Escherichia coli lipopolysaccharide (LPS), followed by the challenge with C...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29238324/immunopathogenesis-and-virus-host-interactions-of-enterovirus-71-in-patients-with-hand-foot-and-mouth-disease
#16
REVIEW
Jonathan A Cox, Julian A Hiscox, Tom Solomon, Mong-How Ooi, Lisa F P Ng
Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29238017/-the-interface-between-the-immune-system-and-autonomic-nervous-system
#17
Shunya Nakane, Akihiro Mukaino, Yukio Ando
  The nervous system and the immune system are two major systems in human body. Although it was revealed these two systems correlated, the control of immune cell dynamics by the nervous system has come to draw a lot of attention at the present time. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in several animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex", is dependent upon vagus nerve stimulation that inhibits cytokine production and attenuates the inflammation...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29237779/estrogen-receptor-%C3%AE-signaling-exacerbates-immune-mediated-nephropathies-through-alteration-of-metabolic-activity
#18
Chelsea Corradetti, Neelakshi R Jog, Matteo Cesaroni, Michael Madaio, Roberto Caricchio
Glomerulonephritis is one of the most serious manifestations of systemic lupus erythematous (SLE). Because SLE is ≥10 times more common in women, a role for estrogens in disease pathogenesis has long been suspected. Estrogen receptor α (ERα) is highly expressed in renal tissue. We asked whether ERα expression contributes to the development of immune-mediated nephropathies like in lupus nephritis. We tested the overall effects of estrogen receptors on the immune response by immunization with OVA and induction of chronic graft-versus-host disease in female ERα-knockout mice...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#19
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29236160/ethanol-and-cytokines-in-the-central-nervous-system
#20
Marisa Roberto, Reesha R Patel, Michal Bajo
The innate immune system plays a critical role in the ethanol-induced neuroimmune response in the brain. Ethanol initiates the innate immune response via activation of the innate immune receptors Toll-like receptors (TLRs, e.g., TLR4, TLR3, TLR7) and NOD-like receptors (inflammasome NLRs) leading to a release of a plethora of chemokines and cytokines and development of the innate immune response. Cytokines and chemokines can have pro- or anti-inflammatory properties through which they regulate the immune response...
December 14, 2017: Handbook of Experimental Pharmacology
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