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https://www.readbyqxmd.com/read/29455927/fibroblast-heterogeneity-and-immunosuppressive-environment-in-human-breast-cancer
#1
Ana Costa, Yann Kieffer, Alix Scholer-Dahirel, Floriane Pelon, Brigitte Bourachot, Melissa Cardon, Philemon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andrei Zinovyev, Anne-Marie Givel, Maria-Carla Parrini, Vassili Soumelis, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+ CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25High FOXP3High , through B7H3, CD73, and DPP4...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29453412/pulmonary-antigen-encounter-regulates-the-establishment-of-tissue-resident-cd8-memory-t-cells-in-the-lung-airways-and-parenchyma
#2
Sean R McMaster, Alexander N Wein, Paul R Dunbar, Sarah L Hayward, Emily K Cartwright, Timothy L Denning, Jacob E Kohlmeier
Resident memory CD8 T (T RM ) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 T RM . Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 T RM establishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment...
February 16, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29449904/expression-profiling-of-chromatin-modifying-enzymes-and-global-dna-methylation-in-cd4-t-cells-from-patients-with-chronic-hiv-infection-at-different-hiv-control-and-progression-states
#3
Roberta Nicoleta Bogoi, Alicia de Pablo, Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, Helem Haydee Vilchez-Rueda, Victor Asensi, Rosa Rodriguez, Victor Toledano, Berta Rodés
Background: Integration of human immunodeficiency virus type 1 (HIV-1) into the host genome causes global disruption of the chromatin environment. The abundance level of various chromatin-modifying enzymes produces these alterations and affects both the provirus and cellular gene expression. Here, we investigated potential changes in enzyme expression and global DNA methylation in chronically infected individuals with HIV-1 and compared these changes with non-HIV infected individuals...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29447265/dynamic-remodeling-of-lipids-coincides-with-dengue-virus-replication-in-the-midgut-of-aedes-aegypti-mosquitoes
#4
Nunya Chotiwan, Barbara G Andre, Irma Sanchez-Vargas, M Nurul Islam, Jeffrey M Grabowski, Amber Hopf-Jannasch, Erik Gough, Ernesto Nakayasu, Carol D Blair, John T Belisle, Catherine A Hill, Richard J Kuhn, Rushika Perera
We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29445761/oxidative-stress-assays-arsenite-and-tbhp-in-caenorhabditis-elegans
#5
Collin Yvès Ewald, John M Hourihan, T Keith Blackwell
Cells and organisms face constant exposure to reactive oxygen species (ROS), either from the environment or as a by-product from internal metabolic processes. To prevent cellular damage from ROS, cells have evolved detoxification mechanisms. The activation of these detoxification mechanisms and their downstream responses represent an overlapping defense response that can be tailored to different sources of ROS to adequately adapt and protect cells. In this protocol, we describe how to measure the sensitivity to oxidative stress from two different sources, arsenite and tBHP, using the nematode C...
July 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29445379/contribution-of-regulatory-t-cells-in-nucleotide-binding-oligomerization-domain-2-response-to-influenza-virus-infection
#6
Benoit Egarnes, Jean Gosselin
Influenza A virus (IAV) is recognized to cause severe pulmonary illnesses in humans, particularly in elderly and children. One of the features associated with IAV infection is an excessive lung inflammation due to an uncontrolled immune response. The nucleotide-binding oligomerization domain 2 (NOD2) receptor is known to recognize ssRNA viruses such as IAV, but its role in the inflammatory process during viral infections remains to be clarified. In a previous report, we have shown that activation of NOD2 with muramyl dipeptide (MDP) significantly reduces both viral loads and lung inflammation and also improves pulmonary function during IAV infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29444258/modeling-the-influence-of-seasonal-differences-in-the-hpa-axis-on-synchronization-of-the-circadian-clock-and-cell-cycle
#7
Kamau Pierre, Rohit T Rao, Clara Hartmanshenn, Ioannis P Androulakis
Synchronization of biological functions to environmental signals enables organisms to anticipate and appropriately respond to daily external fluctuations and is critical to the maintenance of homeostasis. Misalignment of circadian rhythms with environmental cues is associated with adverse health outcomes. Cortisol, the downstream effector of hypothalamic-pituitary-adrenal (HPA) activity, facilitates synchronization of peripheral biological processes to the environment. Cortisol levels exhibit substantial seasonal rhythmicity, with peak levels occurring during the short-photoperiod winter months and reduced levels occurring in the long-photoperiod summer season...
February 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29443042/single-cell-microfluidic-analysis-of-bacillus-subtilis
#8
Matthew T Cabeen, Richard Losick
Microfluidic technology overcomes many of the limitations to traditional analytical methods in microbiology. Unlike bulk-culture methods, it offers single-cell resolution and long observation times spanning hundreds of generations; unlike agarose pad-based microscopy, it has uniform growth conditions that can be tightly controlled. Because the continuous flow of growth medium isolates the cells in a microfluidic device from unpredictable variations in the local chemical environment caused by cell growth and metabolism, authentic changes in gene expression and cell growth in response to specific stimuli can be more confidently observed...
January 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29440380/comparative-transcriptome-analysis-reveals-distinct-genetic-modules-associated-with-helios-expression-in-intratumoral-regulatory-t-cells
#9
Kathleen Yates, Kevin Bi, W Nicholas Haining, Harvey Cantor, Hye-Jung Kim
Regulatory T cells (Tregs) are key modulators of immune tolerance, capable of suppressing inflammatory immune responses and promoting nonlymphoid tissue homeostasis. Helios, a transcription factor (TF) that is selectively expressed by Tregs, has been shown to be essential for the maintenance of Treg lineage stability in the face of inflammatory conditions that include autoimmune disease and cancer. Helios-deficient Tregs within tumors acquire effector T cell function and contribute to immune responses against cancer...
February 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29434589/modeling-human-antitumor-responses-in-vivo-using-umbilical-cord-blood-engrafted-mice
#10
REVIEW
Nicholas A Zumwalde, Jenny E Gumperz
Mice engrafted with human immune cells offer powerful in vivo model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, de novo neoplastic transformation of the human B cells can be induced in vivo in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29434354/single-cell-gene-expression-reveals-a-landscape-of-regulatory-t-cell-phenotypes-shaped-by-the-tcr
#11
David Zemmour, Rapolas Zilionis, Evgeny Kiner, Allon M Klein, Diane Mathis, Christophe Benoist
CD4+ T regulatory cells (Treg) are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells that they regulate. To understand this heterogeneity, we combined single-cell RNA-seq, activation reporter and T cell receptor (TCR) analysis to profile thousands of Treg or conventional CD4+FoxP3- T cells (Tconv) from mouse lymphoid organs and human blood. Treg and Tconv pools showed areas of overlap, as resting 'furtive' Tregs with overall similarity to Tconvs or as a convergence of activated states...
February 12, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29433450/pathogen-recognition-by-nk-cells-amplifies-the-pro-inflammatory-cytokine-production-of-monocyte-derived-dc-via-ifn-%C3%AE
#12
Tammy Oth, Thomas H P M Habets, Wilfred T V Germeraad, Marijke I Zonneveld, Gerard M J Bos, Joris Vanderlocht
BACKGROUND: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus...
February 13, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29431692/development-of-asthma-in-inner-city-children-possible-roles-of-mait-cells-and-variation-in-the-home-environment
#13
Shilpi Chandra, Gerhard Wingender, Jason A Greenbaum, Archana Khurana, Amin M Gholami, Anusha-Preethi Ganesan, Michael Rosenbach, Katy Jaffee, James E Gern, Robert Wood, George O'Connor, Megan Sandel, Meyer Kattan, Leonard Bacharier, Alkis Togias, Anthony A Horner, Mitchell Kronenberg
Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including invariant NKT (iNKT) cells and mucosal-associated invariant T (MAIT) cells. iNKT cell involvement in human asthma is controversial, whereas there has been little analysis of MAIT cells. Using peripheral blood cells from 110 participants from the Urban Environment and Childhood Asthma (URECA) birth cohort study, these cells were analyzed for number and function. We determined whether iNKT cell or MAIT cell frequency at 1 y is correlated with the cytokine polarization of mainstream CD4+ T cells and/or the development of asthma by age 7 y...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29428948/ratio-of-immune-response-to-tumor-burden-predicts-survival-via-regulating-functions-of-lymphocytes-and-monocytes-in-diffuse-large-b-cell-lymphoma
#14
Hongfei Ji, Xingjian Niu, Lei Yin, Yiran Wang, Lan Huang, Qijia Xuan, Liru Li, Han Zhang, Jingtong Li, Yue Yang, Weiwei An, Qingyuan Zhang
BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival...
February 2, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29427987/advances-and-evolving-concepts-in-allergic-asthma
#15
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29427855/fungal-synthesis-of-chiral-phosphonic-synthetic-platform-scope-and-limitations-of-the-method
#16
Monika Serafin-Lewańczuk, Magdalena Klimek-Ochab, Małgorzata Brzezińska-Rodak, Ewa Żymańczyk-Duda
Chiral hydroxyphosphonates due to their wide range of biological properties are industrially important chemicals. Chemical synthesis of their optical isomers is expensive, time consuming and not friendly to the environment, so biotransformations are under consideration. Among others, these compounds act as enzymes inhibitors. This makes the bioconversions of phosphonates, especially scaling experiments, hard to perform. Biocatalysis is one of the methods that can be applied in synthesis of optically pure compounds...
February 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29424466/differential-local-tissue-permissiveness-influences-the-final-fate-of-gpr17-expressing-oligodendrocyte-precursors-in-two-distinct-models-of-demyelination
#17
Giusy T Coppolino, Davide Marangon, Camilla Negri, Gianluca Menichetti, Marta Fumagalli, Paolo Gelosa, Leda Dimou, Roberto Furlan, Davide Lecca, Maria P Abbracchio
Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2 xCAG-eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult...
February 9, 2018: Glia
https://www.readbyqxmd.com/read/29422055/calcineurin-a-beta-deficiency-ameliorates-hfd-induced-hypothalamic-astrocytosis-in-mice
#18
Katrin Pfuhlmann, Sonja C Schriever, Beata Legutko, Peter Baumann, Luke Harrison, Dhiraj G Kabra, Emily Violette Baumgart, Matthias H Tschöp, Cristina Garcia-Caceres, Paul T Pfluger
ᅟ: Astrocytosis is a reactive process involving cellular, molecular, and functional changes to facilitate neuronal survival, myelin preservation, blood brain barrier function and protective glial scar formation upon brain insult. The overall pro- or anti-inflammatory impact of reactive astrocytes appears to be driven in a context- and disease-driven manner by modulation of astrocytic Ca2+ homeostasis and activation of Ca2+/calmodulin-activated serine/threonine phosphatase calcineurin. Here, we aimed to assess whether calcineurin is dispensable for astrocytosis in the hypothalamus driven by prolonged high fat diet (HFD) feeding...
February 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29416537/prior-to-peripheral-tolerance-newly-generated-cd4-t-cells-maintain-dangerous-autoimmune-potential-fas-and-perforin-independent-autoimmunity-controlled-by-programmed-death-1
#19
Kristofor K Ellestad, Govindarajan Thangavelu, Yohannes Haile, Jiaxin Lin, Louis Boon, Colin C Anderson
Lymphopenia can result from various factors, including viral infections, clinical interventions, or as a normal property of the fetal/neonatal period. T cells in a lymphopenic environment undergo lymphopenia-induced proliferation (LIP) to fill the available "niche" as defined by peptide-MHC and homeostatic cytokine resources. We recently reported systemic autoimmunity following reconstitution of the lymphoid compartment of Rag1-/- mice with PD-1-/- hematopoietic stem cells or by transfer of thymocytes, but not splenocytes, suggesting that programmed death-1 (PD-1) plays a crucial role in controlling recent thymic emigrants (RTE) and preventing autoimmunity upon their LIP...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29415950/acute-exposure-to-crotonaldehyde-induces-dysfunction-of-immune-system-in-male-wistar-rats
#20
Limeng Wang, Zhihua Yang, Long Xu, Xiujie Pan, Xingyu Liu, Junwei Zhao, Xiang Li, Maoxiang Zhu, Jianping Xie
Crotonaldehyde is a ubiquitous air pollutant in the environment. It is reported to be harmful to the biosystems in vivo and in vitro. The exposure to crotonaldehyde irritates the mucous membranes and induces edema, hyperemia, cell necrosis, inflammation, and acute respiratory distress syndrome in the lungs. However, the effects of crotonaldehyde on the immune system have not been reported. In the present study, 6-8 weeks old male Wistar rats were exposed to crotonaldehyde by intratracheal instillation at doses of 4, 8, and 16 μL/kg body weight (b...
2018: Journal of Toxicological Sciences
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