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https://www.readbyqxmd.com/read/29160519/ex-vivo-t-lymphocyte-chemokine-receptor-phenotypes-in-patients-with-chronic-chagas-disease
#1
Matheus Barbosa de Miranda, Adriene Siqueira de Melo, Mariana Silva Almeida, Silvia Martins Marinho, Wilson Oliveira, Yara de Miranda Gomes
INTRODUCTION: Elucidating the molecules involved in the inflammatory process of chronic Chagas disease may allow identification of treatment targets. METHODS: The ex vivo phenotypic expression of chemokine receptors CCR1, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4, and CXCR5 on the CD4+ and CD8+ T-cells of patients with chronic Chagas cardiomyopathy of varying severity was evaluated using flow cytometry. RESULTS: Differential expression of CD4+CCR3+ and CD8+CCR4+ T-cells was observed in patients with mild cardiac involvement compared, respectively, with patients with severe cardiac and asymptomatic forms of Chagas disease...
September 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#2
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29153094/differences-between-chronic-lymphocytic-leukaemia-and-small-lymphocytic-lymphoma-cells-by-proteomic-profiling-and-snp-microarray-analysis
#3
Jennifer A Tooze, Edita Hamzic, Fenella Willis, Ruth Pettengell
The majority of malignant cells in chronic lymphocytic leukaemia (CLL) circulate in the peripheral blood whereas small lymphocytic lymphoma (SLL) cells reside in tissues. The aim of this study was to detect differences in chemokine receptor expression, DNA single nucleotide polymorphism (SNP) microarray analysis and proteomic profiling to help elucidate why the cells remain in their respective environments. We identified by flow cytometric studies of chemokine receptors and DNA SNP microarray analysis significant differences between cells from CLL and SLL patients...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29150604/transcriptional-signature-of-human-pro-inflammatory-th17-cells-identifies-reduced-il10-gene-expression-in-multiple-sclerosis
#4
Dan Hu, Samuele Notarbartolo, Tom Croonenborghs, Bonny Patel, Ron Cialic, Tun-Hsiang Yang, Dominik Aschenbrenner, Karin M Andersson, Marco Gattorno, Minh Pham, Pia Kivisakk, Isabelle V Pierre, Youjin Lee, Karun Kiani, Maria Bokarewa, Emily Tjon, Nathalie Pochet, Federica Sallusto, Vijay K Kuchroo, Howard L Weiner
We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ(+)IL-17(+) (TH1/17) and IFN-γ(-)IL-17(+) (TH17) CD4(+) T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150407/disease-trends-over-time-and-cd4-ccr5-t-cells-expansion-predict-carotid-atherosclerosis-development-in-patients-with-systemic-lupus-erythematosus
#5
A Baragetti, G A Ramirez, M Magnoni, K Garlaschelli, L Grigore, M Berteotti, I Scotti, E Bozzolo, A Berti, P G Camici, A L Catapano, A A Manfredi, E Ammirati, G D Norata
BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study...
September 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29146996/the-role-of-cxcr3-lrp1-cross-talk-in-the-invasion-of-primary-brain-tumors
#6
Kevin Boyé, Nadège Pujol, Isabel D Alves, Ya-Ping Chen, Thomas Daubon, Yi-Zong Lee, Stephane Dedieu, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Shih-Che Sue, Andreas Bikfalvi, Clotilde Billottet
CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140829/guiding-regulatory-t-cells-to-the-allograft
#7
Caroline Lamarche, Megan K Levings
PURPOSE OF REVIEW: The application of regulatory T cell (Treg) therapy in organ transplantation is actively being pursued using unmodified, typically polyclonal cells. As the results of these ongoing clinical trials emerge, it is time to plan the next wave of clinical trials of Tregs. Here we will review a key strategy to improve Treg effectiveness and reduce side effects, namely increasing Treg specificity - both in terms of antigen recognition and localization to the allograft. RECENT FINDINGS: Study of chemokine signatures accompanying acute rejection has revealed several chemokines that could be targeted to increase Treg homing...
November 14, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#8
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29133294/proinflammatory-t-cell-status-associated-with-early-life-adversity
#9
Martha M C Elwenspoek, Xenia Hengesch, Fleur A D Leenen, Anna Schritz, Krystel Sias, Violetta K Schaan, Sophie B Mériaux, Stephanie Schmitz, Fanny Bonnemberger, Hartmut Schächinger, Claus Vögele, Jonathan D Turner, Claude P Muller
Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73)...
November 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29128673/bi-allelic-irf8-mutation-a-complex-immunodeficiency-syndrome-with-dendritic-cell-deficiency-monocytopenia-and-immune-dysregulation
#10
Venetia Bigley, Sheetal Maisuria, Urszula Cytlak, Laura Jardine, Matthew A Care, Kile Green, Merry Gunawan, Paul Milne, Rachel Dickinson, Sarah Wiscombe, David Parry, Rainer Doffinger, Arian Laurence, Claudia Fonseca Lic, Oda Stoevesandt, Andrew Gennery, Andrew Cant, Reuben Tooze, A John Simpson, Sophie Hambleton, Sinisa Savic, Gina Doody, Matthew Collin
BACKGROUND: Homozygous K108E mutation of interferon regulatory factor 8 (IRF8) is reported to cause dendritic cell and monocyte deficiency. However, more widespread immune dysfunction is predicted from the multiple roles ascribed to IRF8 in immune cell development and function. OBJECTIVE: We sought to describe the effect on hematopoiesis and immunity of compound heterozygous R83C/ R291Q mutation of IRF8, present in a patient with recurrent viral infection, granulo-proliferation and intracerebral calcification...
November 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29125295/structure-activity-relationships-and-biological-characterization-of-a-novel-potent-and-serum-stable-c-x-c-chemokine-receptor-type-4-cxcr4-antagonist
#11
Salvatore Di Maro, Francesco Saverio Di Leva, Anna Maria Trotta, Diego Brancaccio, Luigi Portella, Michela Aurilio, Stefano Tomassi, Anna Messere, Deborah Sementa, Secondo Lastoria, Alfonso Carotenuto, Ettore Novellino, Stefania Scala, Luciana Marinelli
In our ongoing pursuit of CXCR4 antagonists as potential anticancer agents, we recently developed a potent, selective and plasma stable peptide, Ac-Arg-Ala-[D-Cys-Arg-Phe-Phe-Cys]-COOH (3). Nevertheless, this compound was still not enough potent (IC50 ≈ 53 nM) to enter preclinical studies. Thus, a lead-optimization campaign was here undertaken to further improve the binding affinity of 3 while preserving its selectivity and proteolytic stability. Specifically, extensive structure-activity relationships (SARs) investigations were carried out on both its aromatic and disulfide forming amino acids...
November 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29119926/-the-role-of-cxcr3-in-neurological-diseases
#12
Ya-Qun Zhou, Dai-Qiang Liu, Shu-Ping Chen, Jia Sun, Xue-Rong Zhou, Cui Xing, Da-Wei Ye, Yu-Ke Tian
Neurological diseases have become an obvious challenge due to insufficient therapeutic intervention. Therefore, novel drugs for various neurological disorders are in desperate need. Recently, compelling evidence has demonstrated that chemokine receptor CXCR3, which is a G protein-coupled receptor in the CXC chemokine receptor family, may play a pivotal role in the development of neurological diseases. The expression level of CXCR3 in T cells was significantly elevated in several neurological diseases, suggesting a potential therapeutic role of CXCR3 antagonists...
November 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29116188/cxcl10-cxcr3-axis-is-associated-with-disease-activity-and-the-development-of-mucocutaneous-lesions-in-patients-with-beh%C3%A3-et-s-disease
#13
Sang Jin Lee, Shin Eui Kang, Eun Ha Kang, Byoong Yong Choi, Katherine Masek-Hammerman, Jameel Syed, Yutian Zhan, Kathleen Neff-Phillips, Jin Kyun Park, Eun Young Lee, Eun Bong Lee, Yeong Wook Song
The objective of this study was to investigate CXC chemokines and its receptor in patients with Behcet's disease (BD) and their associations with disease activity. Blood samples were collected from 109 BD patients and 36 age- and sex-matched healthy controls (HCs). Twenty-two follow-up blood samples were collected in BD patients. Serum CXC chemokines (CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13 and CXCL16) and cell surface marker expression (CD3, CD4 and CXCR3) in peripheral blood mononuclear cells (PBMCs) were assayed...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115683/role-of-chemokines-and-the-corresponding-receptors-in-vitiligo-a-pilot-study
#14
Lingling Yang, Sailing Yang, Jiehao Lei, Wenting Hu, Rong Chen, Fuquan Lin, Ai-E Xu
To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-γ or tumor necrosis factor (TNF)-α were tested by quantitative real-time polymerase chain reaction and Luminex...
November 8, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/29113976/co-infection-with-chikungunya-virus-alters-trafficking-of-pathogenic-cd8-t-cells-into-the-brain-and-prevents-plasmodium-induced-neuropathology
#15
Teck-Hui Teo, Shanshan W Howland, Carla Claser, Sin Yee Gun, Chek Meng Poh, Wendy Wl Lee, Fok-Moon Lum, Lisa Fp Ng, Laurent Rénia
Arboviral diseases have risen significantly over the last 40 years, increasing the risk of co-infection with other endemic disease such as malaria. However, nothing is known about the impact arboviruses have on the host response toward heterologous pathogens during co-infection. Here, we investigate the effects of Chikungunya virus (CHIKV) co-infection on the susceptibility and severity of malaria infection. Using the Plasmodium berghei ANKA (PbA) experimental cerebral malaria (ECM) model, we show that concurrent co-infection induced the most prominent changes in ECM manifestation...
November 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29097494/gut-microbiome-influences-efficacy-of-pd-1-based-immunotherapy-against-epithelial-tumors
#16
Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie P M Duong, Maryam Tidjani Alou, Romain Daillère, Aurélie Fluckiger, Meriem Messaoudene, Conrad Rauber, Maria P Roberti, Marine Fidelle, Caroline Flament, Vichnou Poirier-Colame, Paule Opolon, Christophe Klein, Kristina Iribarren, Laura Mondragón, Nicolas Jacquelot, Bo Qu, Gladys Ferrere, Céline Clémenson, Laura Mezquita, Jordi Remon Masip, Charles Naltet, Solenn Brosseau, Coureche Kaderbhai, Corentin Richard, Hira Rizvi, Florence Levenez, Nathalie Galleron, Benoit Quinquis, Nicolas Pons, Bernhard Ryffel, Véronique Minard-Colin, Patrick Gonin, Jean-Charles Soria, Eric Deutsch, Yohann Loriot, François Ghiringhelli, Gérard Zalcman, François Goldwasser, Bernard Escudier, Matthew D Hellmann, Alexander Eggermont, Didier Raoult, Laurence Albiges, Guido Kroemer, Laurence Zitvogel
Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade...
November 2, 2017: Science
https://www.readbyqxmd.com/read/29097419/differential-expression-of-homing-receptor-ligands-on-tumor-associated-vasculature-that-control-cd8-effector-t-cell-entry
#17
Amber N Woods, Ashley L Wilson, Nithya Srivinisan, Jianhao Zeng, Arun B Dutta, J David Peske, Eric F Tewalt, Randal K Gregg, Andrew R Ferguson, Victor H Engelhard
Although CD8+ T cells are critical for controlling tumors, how they are recruited and home to primary and metastatic lesions is incompletely understood. We characterized the homing receptor (HR) ligands on tumor vasculature to determine what drives their expression and their role in T cell entry. The anatomic location of B16-OVA tumors affected the expression of E-selectin, MadCAM-1, and VCAM-1, whereas the HR ligands CXCL9 and ICAM-1 were expressed on the vasculature regardless of location. VCAM-1 and CXCL9 expression was induced by IFNgamma-secreting adaptive immune cells...
November 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29083052/skewed-invariant-natural-killer-t-inkt-cells-impaired-inkt-b-cell-help-and-decreased-sap-expression-in-blood-lymphocytes-from-patients-with-common-variable-immunodeficiency
#18
L V Erazo-Borrás, J A Álvarez-Álvarez, C A Perez-Romero, J C Orrego-Arango, J L Franco-Restrepo, C M Trujillo-Vargas
Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+...
September 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29072682/c-x-c-motif-chemokine-ligand-10-produced-by-mouse-sertoli-cells-in-response-to-mumps-virus-infection-induces-male-germ-cell-apoptosis
#19
Qian Jiang, Fei Wang, Lili Shi, Xiang Zhao, Maolei Gong, Weihua Liu, Chengyi Song, Qihan Li, Yongmei Chen, Han Wu, Daishu Han
Mumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29056444/long-lived-tissue-resident-hiv-1-specific-memory-cd8-t-cells-are-generated-by-skin-immunization-with-live-virus-vectored-microneedle-arrays
#20
Marija Zaric, Pablo Daniel Becker, Catherine Hervouet, Petya Kalcheva, Barbara Ibarzo Yus, Clement Cocita, Lauren Alexandra O'Neill, Sung-Yun Kwon, Linda Sylvia Klavinskis
The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin...
October 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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