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https://www.readbyqxmd.com/read/28215281/emerging-major-histocompatibility-complex-class-i-related-functions-of-nlrc5
#1
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-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#2
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) 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. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 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
#3
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
#4
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 to the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh)...
January 18, 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
#5
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
#6
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 28, 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
#7
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
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#8
Anthony C Y Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the MHC-II to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27793879/cml-cells-actively-evade-host-immune-surveillance-through-cytokine-mediated-downregulation-of-mhc-ii-expression
#9
Anuradha Tarafdar, Lisa E M Hopcroft, Paolo Gallipoli, Francesca Pellicano, Jennifer Cassels, Alan Hair, Koorosh Korfi, Heather G Jørgensen, David Vetrie, Tessa L Holyoake, Alison M Michie
Targeting the fusion oncoprotein BCR-ABL with tyrosine kinase inhibitors has significantly impacted on chronic myeloid leukemia (CML) treatment, transforming the life expectancy of patients; however the risk of relapse remains, due to persistence of leukemic stem cells (LSCs). Therefore it is imperative to explore the mechanisms that result in LSC survival and develop new therapeutic approaches. We now show that MHC-II and its master regulator class II transactivator (CIITA) are downregulated in CML compared to non-CML stem/progenitor cells in a BCR-ABL kinase independent manner...
October 28, 2016: Blood
https://www.readbyqxmd.com/read/27765819/brucella-abortus-down-regulates-mhc-class-ii-by-the-il-6-dependent-inhibition-of-ciita-through-the-downmodulation-of-ifn-regulatory-factor-1-irf-1
#10
Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Aldana Trotta, Pablo Fernández, Roberto G Pozner, Roland Lang, Luciana Balboa, Guillermo H Giambartolomei, Paula Barrionuevo
Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4(+) T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B...
October 20, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27764126/upregulation-of-hla-expression-in-primary-uveal-melanoma-by-infiltrating-leukocytes
#11
T Huibertus van Essen, Sake I van Pelt, Inge H G Bronkhorst, Mieke Versluis, Fariba Némati, Cécile Laurent, Gregorius P M Luyten, Thorbald van Hall, Peter J van den Elsen, Pieter A van der Velden, Didier Decaudin, Martine J Jager
INTRODUCTION: Uveal melanoma (UM) with an inflammatory phenotype, characterized by infiltrating leukocytes and increased human leukocyte antigen (HLA) expression, carry an increased risk of death due to metastases. These tumors should be ideal for T-cell based therapies, yet it is not clear why prognostically-infaust tumors have a high HLA expression. We set out to determine whether the level of HLA molecules in UM is associated with other genetic factors, HLA transcriptional regulators, or microenvironmental factors...
2016: PloS One
https://www.readbyqxmd.com/read/27720955/hic1-epigenetically-represses-ciita-transcription-in-b-lymphocytes
#12
Sheng Zeng, Yuyu Yang, Xian Cheng, Bisheng Zhou, Ping Li, Yuhao Zhao, Xiaocen Kong, Yong Xu
Differentiation of B lymphocytes into isotope-specific plasma cells represents a hallmark event in adaptive immunity. During B cell maturation, expression of the class II transactivator (CIITA) gene is down-regulated although the underlying epigenetic mechanism is not completely defined. Here we report that hypermethylated in cancer 1 (HIC1) was up-regulated in differentiating B lymphocytes paralleling CIITA repression. Over-expression of HIC1 directly repressed endogenous CIITA transcription in B cells. Reporter assay and chromatin immunoprecipitation (ChIP) assay confirmed that HIC1 bound to the proximal CIITA type III promoter (-545/-113); mutation of a conserved HIC1 site within this region abrogated CIITA trans-repression...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27509880/combination-of-the-histone-deacetylase-inhibitor-depsipeptide-and-5-fluorouracil-upregulates-major-histocompatibility-complex-class-ii-and-p21-genes-and-activates-caspase-3-7-in-human-colon-cancer-hct-116-cells
#13
Kouji Okada, Shuko Hakata, Jun Terashima, Toshie Gamou, Wataru Habano, Shogo Ozawa
Epigenetic anticancer drugs such as histone deacetylase (HDAC) inhibitors have been combined with existing anticancer drugs for synergistic or additive effects. In the present study, we found that a very low concentration of depsipeptide, an HDAC inhibitor, potentiated the antitumor activity of 5-fluorouracil (5-FU) in a human colon cancer cell model using HCT-116, HT29, and SW48 cells via the inhibition of colony formation ability or cellular viability. Exposure to a combination of 5-FU (1.75 µM) and 1 nM depsipeptide for 24 and 48 h resulted in a 3- to 4-fold increase in activated caspase-3/7, while 5-FU alone failed to activate caspase-3/7...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27484032/rapid-molecular-diagnostics-of-severe-primary-immunodeficiency-determined-by-using-targeted-next-generation-sequencing
#14
Hui Yu, Victor Wei Zhang, Asbjørg Stray-Pedersen, Imelda Celine Hanson, Lisa R Forbes, M Teresa de la Morena, Ivan K Chinn, Elizabeth Gorman, Nancy J Mendelsohn, Tamara Pozos, Wojciech Wiszniewski, Sarah K Nicholas, Anne B Yates, Lindsey E Moore, Knut Erik Berge, Hanne Sorte, Diana K Bayer, Daifulah ALZahrani, Raif S Geha, Yanming Feng, Guoli Wang, Jordan S Orange, James R Lupski, Jing Wang, Lee-Jun Wong
BACKGROUND: Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management. OBJECTIVE: We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting...
October 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27436580/an-extended-genome-wide-association-study-identifies-novel-susceptibility-loci-for-nasopharyngeal-carcinoma
#15
Qian Cui, Qi-Sheng Feng, Hao-Yuan Mo, Jian Sun, Yun-Fei Xia, Hongxing Zhang, Jia Nee Foo, Yun-Miao Guo, Li-Zhen Chen, Ming Li, Wen-Sheng Liu, Miao Xu, Gangqiao Zhou, Fuchu He, Xueqing Yu, Wei-Hua Jia, Jianjun Liu, Yi-Xin Zeng, Jin-Xin Bei
To further identify novel susceptibility loci of nasopharyngeal carcinoma (NPC), we here extended our previous genome-wide association study (GWAS) by boosting statistical power with larger sample size and validating more SNPs in the ranking list based on the GWAS P-values. The discovery stage consisting of 463,250 SNPs in 1,583 cases and 2,979 controls of southern Chinese ancestry revealed 1,257 top SNPs to be associated with NPC, which were brought forward for validation in 1,925 cases and 1,947 controls of southern Chinese...
August 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27331013/association-of-evi5-rs11808092-cd58-rs2300747-and-ciita-rs3087456-polymorphisms-with-multiple-sclerosis-risk-a-meta-analysis
#16
Jiahe Liu, Xu Liu, Yong Liu, Shimin Deng, Hongbin Huang, Qicong Chen, Weidong Liu, Zunnan Huang
PURPOSE: Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system with a strong genetic component. Previous studies have reported that the association of EVI5 rs11808092, CD58 rs2300747, and CIITA rs3087456 polymorphisms with the susceptibility to MS. However, the results were inconsistent. Thus, we conducted this meta-analysis to provide a more accurate estimation of the association between any of these polymorphisms and MS risk. METHODS: The PubMed, Embase, Chinese National Knowledge Infrastructure, Wan Fang databases and MSGene were used to search all potentially relevant studies...
September 2016: Meta Gene
https://www.readbyqxmd.com/read/27221978/class-ii-transactivator-knockdown-limits-major-histocompatibility-complex-ii-expression-diminishes-immune-rejection-and-improves-survival-of-allogeneic-bone-marrow-stem-cells-in-the-infarcted-heart
#17
Xi-Ping Huang, Ana Ludke, Sanjiv Dhingra, Jian Guo, Zhuo Sun, Li Zhang, Richard D Weisel, Ren-Ke Li
This study was performed to investigate how to overcome immunorejection associated with allogeneic stem cell therapy in the infarcted heart. Allogeneic bone marrow mesenchymal stem cell (MSC) differentiation increases major histocompatibility complex II (MHC II) expression, inducing transition from immunoprivileged to immunogenic phenotype. MHC II expression is regulated by the class II transactivator (CIITA). We isolated and characterized mouse and human MSCs and knocked down CIITA expression. Wild-type (WT) or CIITA-knockout (CIITA(-)) mouse MSCs were implanted into infarcted mouse myocardia, and recipient allo-antibody formation, cell survival, and cardiac function were measured...
September 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27211051/from-genetic-predisposition-to-molecular-mechanisms-of-autoimmune-primary-adrenal-insufficiency
#18
Alberto Falorni, Annalisa Brozzetti, Roberto Perniola
Autoimmune Addison's disease (AAD) is a complex disease that results from the interaction of a predisposing genetic background with still unknown environmental factors. Pathogenic variants in the autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrine syndrome type 1, of which AAD is a major disease component. Among the genetic factors for isolated AAD and autoimmune polyendocrine syndrome type 2, a key role is played by HLA class II genes: HLA-DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*04-DQA1*0301-DQB1*0302 are positively, and DRB1*0403 is negatively, associated with genetic risk for AAD...
2016: Frontiers of Hormone Research
https://www.readbyqxmd.com/read/27207558/adrenomedullin-2-improves-early-obesity-induced-adipose-insulin-resistance-by-inhibiting-the-class-ii-mhc-in-adipocytes
#19
Song-Yang Zhang, Ying Lv, Heng Zhang, Song Gao, Ting Wang, Juan Feng, Yuhui Wang, George Liu, Ming-Jiang Xu, Xian Wang, Changtao Jiang
MHC class II (MHCII) antigen presentation in adipocytes was reported to trigger early adipose inflammation and insulin resistance. However, the benefits of MHCII inhibition in adipocytes remain largely unknown. Here, we showed that human plasma polypeptide adrenomedullin 2 (ADM2) levels were negatively correlated with HOMA of insulin resistance in obese human. Adipose-specific human ADM2 transgenic (aADM2-tg) mice were generated. The aADM2-tg mice displayed improvements in high-fat diet-induced early adipose insulin resistance...
August 2016: Diabetes
https://www.readbyqxmd.com/read/27190335/genotypic-and-phenotypic-predictors-of-inflammation-in-patients-with-chronic-kidney-disease
#20
Karin Luttropp, Malgorzata Debowska, Tomasz Lukaszuk, Leon Bobrowski, Juan Jesus Carrero, Abdul Rashid Qureshi, Peter Stenvinkel, Bengt Lindholm, Jacek Waniewski, Louise Nordfors
BACKGROUND: In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD...
December 2016: Nephrology, Dialysis, Transplantation
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