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https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#1
Caroline Rouger, Sylvain Pagie, Séverine Derbré, Anne-Marie Le Ray, Pascal Richomme, Béatrice Charreau
Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i...
2016: PloS One
https://www.readbyqxmd.com/read/27895918/classical-and-non-classical-hla-class-i-aberrations-in-primary-cervical-squamous-and-adenocarcinomas-and-paired-lymph-node-metastases
#2
Debbie M Ferns, A Marijne Heeren, Sanne Samuels, Maaike C G Bleeker, Tanja D de Gruijl, Gemma G Kenter, Ekaterina S Jordanova
BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27871782/association-of-high-hla-e-expression-during-acute-cellular-rejection-and-numbers-of-hla-class-i-leader-peptide-mismatches-with-reduced-renal-allograft-survival
#3
Hana Guberina, Vera Rebmann, Bettina Wagner, Fabiola da Silva Nardi, Phillip Dziallas, Sebastian Dolff, Anja Bienholz, Jeremias Wohlschlaeger, Agnes Bankfalvi, Falko M Heinemann, Oliver Witzke, Yvonne M Zoet, Frans H J Claas, Peter A Horn, Andreas Kribben, Ilias I N Doxiadis
Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27868107/class-i-hla-haplotypes-form-two-schools-that-educate-nk-cells-in-different-ways
#4
Amir Horowitz, Zakia Djaoud, Neda Nemat-Gorgani, Jeroen Blokhuis, Hugo G Hilton, Vivien Béziat, Karl-Johan Malmberg, Paul J Norman, Lisbeth A Guethlein, Peter Parham
Natural killer (NK) cells are lymphocytes having vital functions in innate and adaptive immunity, as well as placental reproduction. Controlling education and functional activity of human NK cells are various receptors that recognize HLA class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C are recognized by equally diverse killer cell immunoglobulin-like receptors (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C must bind to HLA-E for it to become a ligand for the conserved CD94:NKG2A receptor...
September 2016: Science Immunology
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#5
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27853650/therapeutic-cd94-nkg2a-blockade-improves-natural-killer-cell-dysfunction-in-chronic-lymphocytic-leukemia
#6
Emily M McWilliams, Jennifer M Mele, Carolyn Cheney, Elizabeth A Timmerman, Faraz Fiazuddin, Ethan J Strattan, Xiaokui Mo, John C Byrd, Natarajan Muthusamy, Farrukh T Awan
Natural killer (NK)-cell count is predictive of chronic lymphoid leukemia (CLL) disease progression and their dysfunction is well documented, but the etiology of this is currently lacking. CLL cells have been shown to over-express HLA-E, the natural ligand for NKG2A expressed on NK-cells that generates a distinct negative signal relative to direct NK-cell cytotoxicity in other disease models. Utilizing a novel anti-NKG2A monoclonal blocking antibody (mAb), monalizumab, we explored the in vitro preclinical activity of targeting the NKG2A receptor, and the NKG2A/HLA-E interaction as a mechanism of tumor evasion in CLL patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27806848/a-comparison-of-cancer-stem-cell-markers-and-nonclassical-major-histocompatibility-complex-antigens-in-colorectal-tumor-and-noncancerous-tissues
#7
Rabia Bilge Özgül Özdemir, Alper Tunga Özdemir, Fatih Oltulu, Kamile Kurt, Gürkan Yiğittürk, Cengiz Kırmaz
Colorectal carcinoma (CRC) is one of the most fatal types of cancer in both women and men, and, unfortunately, patients are often diagnosed at an advanced stage. Cancer stem cells (CSCs) are associated with poor prognosis, metastasis, and recurrence, as well as chemotherapy and radiotherapy resistance. Therefore, different treatment alternatives are needed to facilitate the elimination of CSCs. One such approach is immunotherapy; however, tumor cells can evade immune cells by alteration of the expression patterns of human leukocyte antigens (HLA)...
December 2016: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/27801784/the-activating-nkg2c-receptor-is-significantly-reduced-in-nk-cells-after-allogeneic-stem-cell-transplantation-in-patients-with-severe-graft-versus-host-disease
#8
Lambros Kordelas, Nina-Kristin Steckel, Peter A Horn, Dietrich W Beelen, Vera Rebmann
Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E)...
October 27, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27796368/targeting-non-classical-myelin-epitopes-to-treat-experimental-autoimmune-encephalomyelitis
#9
Xiaohua Wang, Jintao Zhang, David J Baylink, Chih-Huang Li, Douglas M Watts, Yi Xu, Xuezhong Qin, Michael H Walter, Xiaolei Tang
Qa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8(+) regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27783105/high-efficiency-lysis-of-cervical-cancer-by-allogeneic-nk-cells-derived-from-umbilical-cord-progenitors-is-independent-of-hla-status
#10
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
October 25, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27716848/follicular-regulatory-cd8-t-cells-impair-the-germinal-center-response-in-siv-and-ex-vivo-hiv-infection
#11
Brodie Miles, Shannon M Miller, Joy M Folkvord, David N Levy, Eva G Rakasz, Pamela J Skinner, Elizabeth Connick
During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27714943/is-hla-e-a-possible-genetic-marker-relevant-for-natural-conception
#12
Georgia Fernanda Gelmini, Cynthia Hernandes Costa, Fabiola da Silva Nardi, Pryscilla Fanini Wowk, Sibelle Botogosque Mattar, Alessandro Schuffner, Maria da Graça Bicalho, Valéria Maria Munhoz Sperandio Roxo
BACKGROUND: HLA-E products, class Ib human leukocyte antigens, act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy. AIMS: To evaluate HLA-E role in the establishment of a viable pregnancy. MATERIALS & METHODS: HLA-E was genotyped by sequence-based typing (SBT) and analyzed for specific polymorphisms, comparing couples who underwent assisted reproduction treatment (ART) and fertile control couples...
December 2016: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/27701438/association-of-hla-a-and-non-classical-hla-class-i-alleles
#13
Federico Carlini, Virginia Ferreira, Stéphane Buhler, Audrey Tous, Jean-François Eliaou, Céline René, Jacques Chiaroni, Christophe Picard, Julie Di Cristofaro
The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors...
2016: PloS One
https://www.readbyqxmd.com/read/27699181/characteristics-of-hla-e-restricted-t-cell-responses-and-their-role-in-infectious-diseases
#14
Simone A Joosten, Lucy C Sullivan, Tom H M Ottenhoff
Human HLA-E can, in addition to self-antigens, also present pathogen-derived sequences, which elicit specific T-cell responses. T-cells recognize their antigen presented by HLA-E highly specifically and have unique functional and phenotypical properties. Pathogen specific HLA-E restricted CD8(+) T-cells are an interesting new player in the field of immunology. Future work should address their exact roles and relative contributions in the immune response against infectious diseases.
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27610393/soluble-hla-g-and-hla-e-levels-in-bone-marrow-plasma-samples-are-related-to-disease-stage-in-neuroblastoma-patients
#15
Fabio Morandi, Sarah Pozzi, Barbara Carlini, Loredana Amoroso, Vito Pistoia, Maria Valeria Corrias
The role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27596021/distribution-of-hla-g-extended-haplotypes-and-one-hla-e-polymorphism-in-a-large-scale-study-of-mother-child-dyads-with-and-without-severe-preeclampsia-and-eclampsia
#16
L L Nilsson, S Djurisic, A-M N Andersen, M Melbye, D Bjerre, L Ferrero-Miliani, R Hackmon, D E Geraghty, T V F Hviid
The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants...
October 2016: HLA
https://www.readbyqxmd.com/read/27589686/hla-e-expression-and-its-clinical-relevance-in-human-renal-cell-carcinoma
#17
Barbara Seliger, Simon Jasinski-Bergner, Dagmar Quandt, Christine Stoehr, Juergen Bukur, Sven Wach, Wolfgang Legal, Helge Taubert, Bernd Wullich, Arndt Hartmann
The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and -C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance. While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27589570/prognostic-value-of-pdl1-expression-in-pancreatic-cancer
#18
David J Birnbaum, Pascal Finetti, Alexia Lopresti, Marine Gilabert, Flora Poizat, Olivier Turrini, Jean-Luc Raoul, Jean-Robert Delpero, Vincent Moutardier, Daniel Birnbaum, Emilie Mamessier, François Bertucci
Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples...
August 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27585642/genome-wide-dna-methylation-patterns-in-cd4-t-cells-from-chinese-han-patients-with-rheumatoid-arthritis
#19
Shicheng Guo, Qi Zhu, Ting Jiang, Rongsheng Wang, Yi Shen, Xiao Zhu, Yan Wang, Fengmin Bai, Qin Ding, Xiaodong Zhou, Guangjie Chen, Dong Yi He
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. METHOD: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray...
September 1, 2016: Modern Rheumatology
https://www.readbyqxmd.com/read/27572969/hiv-host-interactome-revealed-directly-from-infected-cells
#20
Yang Luo, Erica Y Jacobs, Todd M Greco, Kevin D Mohammed, Tommy Tong, Sarah Keegan, James M Binley, Ileana M Cristea, David Fenyö, Michael P Rout, Brian T Chait, Mark A Muesing
Although genetically compact, HIV-1 commandeers vast arrays of cellular machinery to sustain and protect it during cycles of viral outgrowth. Transposon-mediated saturation linker scanning mutagenesis was used to isolate fully replication-competent viruses harbouring a potent foreign epitope tag. Using these viral isolates, we performed differential isotopic labelling and affinity-capture mass spectrometric analyses on samples obtained from cultures of human lymphocytes to classify the vicinal interactomes of the viral Env and Vif proteins as they occur during natural infection...
May 23, 2016: Nature Microbiology
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