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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
#1
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
#2
Anthony Cy Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the major histocompatibility complex class II (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 variation in C2ta has 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
July 19, 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
#10
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
#11
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
#12
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
#13
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
#14
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...
April 19, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27144640/quantitative-real-time-polymerase-chain-reaction-measurement-of-hla-dra-gene-expression-in-whole-blood-is-highly-reproducible-and-shows-changes-that-reflect-dynamic-shifts-in-monocyte-surface-hla-dr-expression-during-the-course-of-sepsis
#15
Sara Cajander, Elisabet Tina, Anders Bäckman, Anders Magnuson, Kristoffer Strålin, Bo Söderquist, Jan Källman
INTRODUCTION: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)...
2016: PloS One
https://www.readbyqxmd.com/read/27105023/role-of-pu-1-in-mhc-class-ii-expression-via-ciita-transcription-in-plasmacytoid-dendritic-cells
#16
Ryosuke Miura, Kazumi Kasakura, Nobuhiro Nakano, Mutsuko Hara, Keiko Maeda, Ko Okumura, Hideoki Ogawa, Takuya Yashiro, Chiharu Nishiyama
The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific expression of CIITA have been identified. Although the MHC class II expression in plasmacytoid dendritic cells (pDCs) is also mediated by CIITA, the transcription factors involved in the CIITA expression in pDCs are largely unknown. In the present study, we analyzed the role of a hematopoietic lineage-specific transcription factor, PU.1, in CIITA transcription in pDCs. The introduction of PU...
2016: PloS One
https://www.readbyqxmd.com/read/27101876/plzf-innate-t-cells-support-the-tgf-%C3%AE-dependent-generation-of-activated-memory-like-regulatory-t-cells
#17
Byung Hyun Kang, Hyo Jin Park, Hi Jung Park, Jae-Ii Lee, Seong Hoe Park, Kyeong Cheon Jung
PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether PLZF(+) innate T cells also affect the development and function of Foxp3(+) regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant PLZF(+) CD4 T cells and invariant natural killer T cells, respectively, revealed that Foxp3(+) T cells in these mice exhibited a CD103(+) activated/memory-like phenotype...
June 30, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27089879/the-mhc-ii-transactivator-ciita-inhibits-tat-function-and-hiv-1-replication-in-human-myeloid-cells
#18
Greta Forlani, Filippo Turrini, Silvia Ghezzi, Alessandra Tedeschi, Guido Poli, Roberto S Accolla, Giovanna Tosi
BACKGROUND: We previously demonstrated that the HLA class II transactivator CIITA inhibits HIV-1 replication in T cells by competing with the viral transactivator Tat for the binding to Cyclin T1 subunit of the P-TEFb complex. Here, we analyzed the anti-viral function of CIITA in myeloid cells, another relevant HIV-1 target cell type. We sinvestigated clones of the U937 promonocytic cell line, either permissive (Plus) or non-permissive (Minus) to HIV-1 replication. This different phenotype has been associated with the expression of TRIM22 in U937 Minus but not in Plus cells...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27087581/cita-nlrc5-a-critical-transcriptional-regulator-of-mhc-class-i-gene-expression
#19
REVIEW
Isaac Downs, Saptha Vijayan, Tabasum Sidiq, Koichi S Kobayashi
Major histocompatibility complex (MHC) class I and class II molecules play essential roles in the development and activation of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator) has been recognized as a master regulator of MHC class II gene expression, albeit knowledge about the regulatory mechanism of MHC class I gene expression had been limited. Recently identified MHC class I transactivator (CITA), or NLRC5, also belongs to the NLR protein family and constitutes a critical regulator for the transcriptional activation of MHC class I genes...
July 8, 2016: BioFactors
https://www.readbyqxmd.com/read/27010584/identification-of-novel-oncogenic-mutations-in%C3%A2-thyroid-cancer
#20
Susan C Pitt, Roland A Hernandez, Matthew A Nehs, Atul A Gawande, Francis D Moore, Daniel T Ruan, Nancy L Cho
BACKGROUND: Thyroid cancer patients frequently have favorable outcomes. However, a small subset develops aggressive disease refractory to traditional treatments. Therefore, we sought to characterize oncogenic mutations in thyroid cancers to identify novel therapeutic targets that may benefit patients with advanced, refractory disease. STUDY DESIGN: Data on 239 thyroid cancer specimens collected between January 2009 and September 2014 were obtained from the Dana Farber/Brigham and Women's Cancer Center...
June 2016: Journal of the American College of Surgeons
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