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https://www.readbyqxmd.com/read/28498806/epigenetic-modifiers-upregulate-mhc-ii-and-impede-ovarian-cancer-tumor-growth
#1
Taylor B Turner, Selene Meza-Perez, Angelina Londoño, Ashwini Katre, Jacelyn E Peabody, Haller J Smith, Andres Forero, Lyse A Norian, J Michael Straughn, Donald J Buchsbaum, Troy D Randall, Rebecca C Arend
Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484267/microrna-146a-reduces-mhc-ii-expression-via-targeting-jak-stat-signaling-in-dendritic-cells-after-stem-cell-transplantation
#2
N Stickel, K Hanke, D Marschner, G Prinz, M Köhler, W Melchinger, D Pfeifer, A Schmitt-Graeff, T Brummer, A Heine, P Brossart, D Wolf, N von Bubnoff, J Finke, J Duyster, J Ferrara, U Salzer, R Zeiser
Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant-recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a(-/-) dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected-DCs ameliorated disease...
May 9, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28483578/mhc-ii-but-not-mhc-ii-hepatic-stellate-cells-contribute-to-liver-fibrosis-of-mice-in-infection-with-schistosoma-japonicum
#3
Chun-Lei Zhou, De-Long Kong, Jin-Feng Liu, Zhong-Kui Lu, Hong-Fei Guo, Wei Wang, Jing-Fan Qiu, Xin-Jian Liu, Yong Wang
Hepatic stellate cells (HSCs) are considered as the main effector cells in vitamin A metabolism and liver fibrosis, as well as in hepatic immune regulation. Recently, researches have revealed that HSCs have plasticity and heterogeneity, which depend on their lobular location and whether liver is normal or injured. This research aimed to explore the biological characteristics and heterogeneity of HSCs in mice with Schistosoma japonicum (S. japonicum) infection, and determine the subpopulation of HSCs in pathogenesis of hepatic fibrosis caused by S...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28479318/identification-of-somatic-mutations-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-by-massive-parallel-sequencing
#4
Sylvain Mareschal, Anne Pham-Ledard, Pierre Julien Viailly, Sydney Dubois, Philippe Bertrand, Catherine Maingonnat, Maxime Fontanilles, Elodie Bohers, Philippe Ruminy, Isabelle Tournier, Philippe Courville, Bernard Lenormand, Anne Bénédicte Duval, Emilie Andrieu, Laurence Verneuil, Beatrice Vergier, Hervé Tilly, Pascal Joly, Thierry Frebourg, Marie Beylot-Barry, Jean-Philippe Merlio, Fabrice Jardin
To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma leg-type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma (DLBCL) subtypes, we analyzed a total cohort of 28 PCLBCL-LT cases by next generation sequencing with a Lymphopanel designed for DLBCL. We also analyzed 12 pairs of tumor and control DNA samples by whole exome sequencing which led us to perform resequencing of three selected genes not included in the Lymphopanel: TBL1XR1, KLHL6 and IKZF3...
May 4, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28424681/the-spontaneous-autoimmune-neuromyopathy-in-icosl-nod-mice-is-cd4-t-cell-and-interferon-%C3%AE-dependent
#5
Claire Briet, Gwladys Bourdenet, Ute C Rogner, Chantal Becourt, Isabelle Tardivel, Laurent Drouot, Christophe Arnoult, Jean-Claude do Rego, Nicolas Prevot, Charbel Massaad, Olivier Boyer, Christian Boitard
Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the development of a spontaneous autoimmune neuromyopathy. At the pathological level, ICOSL(-/-) NOD mice show stronger protection from insulitis than their ICOS(-/-) counterparts. Also, the ICOSL(-/-) NOD model carries a limited C57BL/6 region containing the Icosl nul mutation, but, in contrast to ICOS(-/-) NOD mice, no gene variant previously reported as associated to NOD diabetes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28414303/development-of-potent-class-ii-transactivator-gene-delivery-systems-capable-of-inducing-de-novo-mhc-ii-expression-in-human-cells-in-vitro-and-ex-vivo
#6
M L Palma, P Duangkhae, B Douradinha, I F T Viana, P O Rigato, R Dhalia, R B Mailliard, S M Barratt-Boyes, E J M Nascimento, T M Oshiro, A J da Silva Duarte, E T A Marques
Class II transactivator (CIITA) induces transcription of major histocompatibility complex (MHC) II genes and can potentially be used to improve genetic immunotherapies by converting non-immune cells into cells capable of presenting antigens to CD4(+) T cells. However, CIITA expression is tightly controlled and it remains unclear whether distinct non-immune cells differ in this transactivator regulation. Here we describe the development of gene delivery systems capable of promoting the efficient CIITA expression in non-immune cell lines and in primary human cells of an ex vivo skin explant model...
May 4, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28405623/bcg-vaccination-induces-hiv-target-cell-activation-in-hiv-exposed-infants-in-a-randomized-trial
#7
Melanie A Gasper, Anneke C Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S Passmore, Willem Hanekom, Mark F Cotton, I Nicholas Crispe, Donald L Sodora, Heather B Jaspan
BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4(+) T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28340094/nlrp2-is-a-suppressor-of-nf-%C3%A6-b-signaling-and-hla-c-expression-in-human-trophoblasts%C3%A2-%C3%A2
#8
Tamara Tilburgs, Torsten B Meissner, Leonardo M R Ferreira, Arend Mulder, Kiran Musunuru, Junqiang Ye, Jack L Strominger
During pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of human leukocyte antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E, and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated. The major histocompatibility complex (MHC) class I and class II transcriptional activators NLRC5 and CIITA are expressed neither by EVT nor by the EVT model cell line JEG3, which has an MHC expression pattern identical to that of EVT...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339086/identification-of-novel-mutations-in-endometrial-cancer-patients-by-whole-exome-sequencing
#9
Ya-Sian Chang, Hsien-Da Huang, Kun-Tu Yeh, Jan-Gowth Chang
The aim of the present study was to identify genomic alterations in Taiwanese endometrial cancer patients. This information is vitally important in Taiwan, where endometrial cancer is the second most common gynecological cancer. We performed whole-exome sequencing on DNA from 14 tumor tissue samples from Taiwanese endometrial cancer patients. We used the Genome Analysis Tool kit software package for data analysis, and the dbSNP, Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA) databases for comparisons...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28293932/effect-of-tio%C3%A2-nanoparticles-on-inflammasome-mediated-airway-inflammation-and-responsiveness
#10
Byeong Gon Kim, Pureun Haneul Lee, Sun Hye Lee, Moo Kyun Park, An Soo Jang
PURPOSE: Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (pro-IL-1β) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28286521/pulling-a-ligase-out-of-a-hat-pcaf-mediates-ubiquitination-of-the-class-ii-transactivator
#11
Julie E Morgan, Susanna F Greer
The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the "master regulator" of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region...
2017: International Journal of Cell Biology
https://www.readbyqxmd.com/read/28257690/genetic-regulation-of-adipose-gene-expression-and-cardio-metabolic-traits
#12
Mete Civelek, Ying Wu, Calvin Pan, Chelsea K Raulerson, Arthur Ko, Aiqing He, Charles Tilford, Niyas K Saleem, Alena Stančáková, Laura J Scott, Christian Fuchsberger, Heather M Stringham, Anne U Jackson, Narisu Narisu, Peter S Chines, Kerrin S Small, Johanna Kuusisto, Brian W Parks, Päivi Pajukanta, Todd Kirchgessner, Francis S Collins, Peter S Gargalovic, Michael Boehnke, Markku Laakso, Karen L Mohlke, Aldons J Lusis
Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described...
March 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28228757/regulation-of-epigenetic-modifiers-including-kdm6b-by-interferon-%C3%AE-and-interleukin-4-in-human-macrophages
#13
Gökçe Yıldırım-Buharalıoğlu, Mark Bond, Graciela B Sala-Newby, Charles C T Hindmarch, Andrew C Newby
BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28215281/emerging-major-histocompatibility-complex-class-i-related-functions-of-nlrc5
#14
S T Chelbi, A T Dang, G Guarda
Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are being rapidly unraveled...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibits-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#15
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Kumar Naik, Geetanjali Ganguli, Kali Prasad Pattanaik, Sunil Kumar Raghav, Vinay Kumar Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. M. tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. The M. tuberculosis genome encodes 23 such ESAT-6 family proteins...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28197387/ciita-driven-mhc-class-ii-expressing-tumor-cells-can-efficiently-prime-naive-cd4-th-cells-in-vivo-and-vaccinate-the-host-against-parental-mhc-ii-negative-tumor-cells
#16
Farah Bou Nasser Eddine, Greta Forlani, Letizia Lombardo, Alessandra Tedeschi, Giovanna Tosi, Roberto S Accolla
Our previous studies showed that non-immunogenic H-2(d) tumor cells of distinct epithelial histotypes can become highly immunogenic, induce a protective CD4(+) T cell response and vaccinate the animals against parental MHC-II-negative cells if they are rendered MHC class II-positive by stable transfection with the Air-1-encoded MHC-II transcriptional activator CIITA. These studies did not establish, however, whether tumor immunity was the consequence of a direct priming of naive CD4(+) T lymphocytes by CIITA-driven MHC-II-expressing tumor cells or by MHC-II-tumor antigen complexes engulfed by dendritic cells (DC) and exposed on the surface of these professional antigen presenting cells (APC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28100790/genome-wide-analysis-in-brazilians-reveals-highly-differentiated-native-american-genome-regions
#17
Josyf C Mychaleckyj, Alexandre Havt, Uma Nayak, Relana Pinkerton, Emily Farber, Patrick Concannon, Aldo A Lima, Richard L Guerrant
Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh)...
March 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28094290/protein-arginine-methyltransferase-1-prmt1-represses-mhc-ii-transcription-in-macrophages-by-methylating-ciita
#18
Zhiwen Fan, Jianfei Li, Ping Li, Qing Ye, Huihui Xu, Xiaoyan Wu, Yong Xu
Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27989934/nf-y-and-the-immune-response-dissecting-the-complex-regulation-of-mhc-genes
#19
REVIEW
Nikoleta Sachini, Joseph Papamatheakis
Nuclear Factor Y (NF-Y) was first described as one of the CCAAT binding factors. Although CCAAT motifs were found to be present in various genes, NF-Y attracted a lot of interest early on, due to its role in Major Histocompatibility Complex (MHC) gene regulation. MHC genes are crucial in immune response and show peculiar expression patterns. Among other conserved elements on MHC promoters, an NF-Y binding CCAAT box was found to contribute to MHC transcriptional regulation. NF-Y along with other DNA binding factors assembles in a stereospecific manner to form a multiprotein scaffold, the MHC enhanceosome, which is necessary but not sufficient to drive transcription...
October 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27917375/recombinant-lipoprotein-rv1016c-derived-from-mycobacterium-tuberculosis-is-a-tlr-2-ligand-that-induces-macrophages-apoptosis-and-inhibits-mhc-ii-antigen-processing
#20
Haibo Su, Shenglin Zhu, Lin Zhu, Wei Huang, Honghai Wang, Zhi Zhang, Ying Xu
TLR2-dependent cellular signaling in Mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class II major histocompatibility complex (MHC-II) molecules antigen processing, leading to evasion of surveillance. Mycobacterium tuberculosis (MTB) lipoproteins are an important class of Toll-like receptor (TLR) ligand, and identified as specific components that mediate these effects. In this study, we identified and characterized MTB lipoprotein Rv1016c (lpqT) as a cell wall associated-protein that was exposed on the cell surface and enhanced the survival of recombinants M...
2016: Frontiers in Cellular and Infection Microbiology
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