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Gene expression in lymphocytes

Magdalena Dryglewska, Bogdan Kolarz, Maria Majdan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Yanan Du, Yan Wang, Liqing Du, Chang Xu, Kaihua Ji, Jinhan Wang, Qiang Liu
In this data article, 146 villagers (exposed group) were randomly selected from the workers who involved in the e-wastes recycling directly as a daily job in Tianjin. Control group, including 121 villagers, came from another town without e-waste disposal sites. Chromosomal aberrations (CA) and cytokinesis blocking micronucleus (CBMN) were performed to detect the cytogenetic effect for each subject. DNA damage was detected using comet assay; the DNA percentage in the comet tail (TDNA%), tail moment (TM), and Olive tail moment (OTM) were recorded to describe DNA damage to lymphocytes and spermatozoa...
April 2018: Data in Brief
Gabrielle Bradshaw, Robbie R Lualhati, Cassie L Albury, Neven Maksemous, Deidre Roos-Araujo, Robert A Smith, Miles C Benton, David A Eccles, Rod A Lea, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
Background: We investigated the molecular etiology of a young male proband with confirmed immunodeficiency of unknown cause, presenting with recurrent bacterial and Varicella zoster viral infections in childhood and persistent lymphopenia into early adulthood. Aim: To identify causative functional genetic variants related to an undiagnosed primary immunodeficiency. Method: Whole genome microarray copy number variant (CNV) analysis was performed on the proband followed by whole exome sequencing (WES) and trio analysis of the proband and family members...
2018: Frontiers in Immunology
Martin F Flajnik
The adaptive immune system arose 500 million years ago in ectothermic (cold-blooded) vertebrates. Classically, the adaptive immune system has been defined by the presence of lymphocytes expressing recombination-activating gene (RAG)-dependent antigen receptors and the MHC. These features are found in all jawed vertebrates, including cartilaginous and bony fish, amphibians and reptiles and are most likely also found in the oldest class of jawed vertebrates, the extinct placoderms. However, with the discovery of an adaptive immune system in jawless fish based on an entirely different set of antigen receptors - the variable lymphocyte receptors - the divergence of T and B cells, and perhaps innate-like lymphocytes, goes back to the origin of all vertebrates...
March 19, 2018: Nature Reviews. Immunology
Lina Wang, Wenli Feng, Xiao Yang, Feifei Yang, Rong Wang, Qian Ren, Xiaofan Zhu, Guoguang Zheng
The ubiquitin-proteasome system (UPS) participates in both physiological and pathological processes through the posttranslational regulation of intracellular signal transduction pathways. F-box and WD-40 domain protein 11 (Fbxw11) is a component of the SCF (Skp1-Cul1-F-box) E3 ubiquitin ligase complex. Fbxw11 regulates various signal transduction pathways, and it may have pathological roles in tumorigenesis. However, the role of Fbxw11 in the development of leukemia and the underlying mechanisms remain largely unknown...
March 19, 2018: Cell Death & Disease
Stephen J Holland, Lesley M Berghuis, Justin J King, Lakshminarayan M Iyer, Katarzyna Sikora, Heather Fifield, Sarah Peter, Emma M Quinlan, Fumiaki Sugahara, Prashant Shingate, Inês Trancoso, Norimasa Iwanami, Elena Temereva, Christine Strohmeier, Shigeru Kuratani, Byrappa Venkatesh, Guillaume Evanno, L Aravind, Michael Schorpp, Mani Larijani, Thomas Boehm
Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA /C genes in T-like cells and the VLRB genes in B-like cells, respectively...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
Grant C O'Connell, Madison B Treadway, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n = 3)...
March 17, 2018: Translational Stroke Research
Bryan Ceronie, Benjamin M Jacobs, David Baker, Nicolas Dubuisson, Zhifeng Mao, Francesca Ammoscato, Helen Lock, Hilary J Longhurst, Gavin Giovannoni, Klaus Schmierer
BACKGROUND: The mechanism of action of oral cladribine, recently licensed for relapsing multiple sclerosis, is unknown. OBJECTIVE: To determine whether cladribine depletes memory B cells consistent with our recent hypothesis that effective, disease-modifying treatments act by physical/functional depletion of memory B cells. METHODS: A cross-sectional study examined 40 people with multiple sclerosis at the end of the first cycle of alemtuzumab or injectable cladribine...
March 17, 2018: Journal of Neurology
Sarene Koh, Janine Kah, Christine Y L Tham, Ninghan Yang, Erica Ceccarello, Adeline Chia, Margaret Chen, Atefeh Khakpoor, Andrea Pavesi, Anthony T Tan, Maura Dandri, Antonio Bertoletti
BACKGROUND & AIMS: Strategies to develop virus-specific T cells against hepatic viral infections have been hindered by safety concerns. We engineered non-lytic human T cells to suppress replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) without overt hepatotoxicity, and investigated their antiviral activity. METHODS: We electroporated resting T cells or T cells activated by anti-CD3 with mRNAs encoding HBV or HCV-specific T-cell receptors (TCRs) to create 2 populations of TCR-reprogrammed T cells...
March 14, 2018: Gastroenterology
Verica Paunovic, Irena Vukovic Petrovic, Marina Milenkovic, Kristina Janjetovic, Vera Pravica, Irena Dujmovic, Emina Milosevic, Vanja Martinovic, Sarlota Mesaros, Jelena Drulovic, Vladimir Trajkovic
Autophagy, a process of controlled self-digestion which regulates cell homeostasis, is involved in innate and adaptive immunity. We investigated the expression of autophagy genes and autophagic activity in distinct lymphocyte populations in treatment-naive MS patients. The mRNA and protein levels of autophagy-related (ATG)5, required for autophagosome formation, were increased in CD4+ and CD4- T cells, but not B cells of MS patients compared to control subjects. The expression of other investigated autophagy genes, as well as the autophagic activity, did not significantly differ between the two groups...
March 5, 2018: Journal of Neuroimmunology
Caterina Musolino, Giacomo Oteri, Alessandro Allegra, Manuela Mania, Angela D'Ascola, Angela Avenoso, Vanessa Innao, Andrea Gaetano Allegra, Salvatore Campo
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ...
March 15, 2018: Annals of Hematology
Haiyan Gao, Mei Yang, Xiaolan Zhang
The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation...
April 2018: Oncology Letters
Natalia Anahí Juiz, Irma Torrejón, Marianela Burgos, Ana María Fernanda Torres, Tomás Duffy, Nelly Melina Cayo, Anahí Tabasco, Miriam Salvo, Silvia Andrea Longhi, Alejandro Gabriel Schijman
Infection with Trypanosoma cruzi in women at reproductive age is associated with congenital transmission and adverse pregnancy outcome. The placenta is a key barrier to infection. We characterized gene expression profiles of term placental environment from T. cruzi seropositive (SP) and seronegative (SN) mothers performing RNA-seq. Nine pools of placental RNA paired samples were used: three from SN and six from SP tissues. Each pool consisted of female/male newborns and vaginal/caesarean deliveries binomials...
March 12, 2018: American Journal of Pathology
Yufei Chen, Yannick L Traore, Sidi Yang, Julie Lajoie, Keith R Fowke, Daniel W Rickey, Emmanuel A Ho
Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This "immune quiescent" state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens. Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women-oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an "immune quiescent" state within the FGT for the prevention of HIV infection...
March 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Tiziana Alberio, Greta Forlani, Marta Lualdi, Giovanna Tosi, Roberto S Accolla, Mauro Fasano
BACKGROUND: Fibrinogen is a central player in the blood coagulation cascade and one of the most abundant plasma proteins. This glycoprotein also triggers important events (e.g., cell spreading, the respiratory burst and degranulation) in neutrophil cells via a αM β2 integrin-mediated binding to the cell surface. Yet, little is known about the interaction of fibrinogen with leukocytes other than neutrophils or stimulated monocytes, although high amounts of fibrinogen protein can also be found in lymphocytes, particularly in T-cells...
March 14, 2018: Journal of Translational Medicine
Jiaqiang Ren, Dawn Ward, Steven Chen, Katherine Tran, Ping Jin, Marianna Sabatino, Pamela G Robey, David F Stroncek
BACKGROUND: Bone marrow stromal cells (BMSCs) have classically been cultured in media supplemented with fetal bovine serum (FBS). As an alternative to FBS, pooled solvent detergent apheresis platelets, HPGF-C18, was evaluated for BMSC culture. METHODS: A comparison of passage 2 BMSC growth revealed that 10% HPGF-C18 produced similar cell numbers as 20% FBS. Marrow aspirates from 5 healthy subjects were cultured for 4 passages in 10% HPGF-C18 or 20% FBS and were analyzed for proliferation, colony formation efficiency (CFE), surface marker expression, suppression of mixed lymphocyte reactions (MLRs), global gene and microRNA expression analysis...
March 14, 2018: Journal of Translational Medicine
Tafadzwa Mlambo, Sandra Nitsch, Markus Hildenbeutel, Marianna Romito, Maximilian Müller, Claudia Bossen, Sven Diederichs, Tatjana I Cornu, Toni Cathomen, Claudio Mussolino
Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have established a novel platform for achieving precision epigenome editing using designer epigenome modifiers (DEMs). DEMs combine in a single molecule a DNA binding domain based on highly specific transcription activator-like effectors (TALEs) and several effector domains capable of inducing DNA methylation and locally altering the chromatin structure to silence target gene expression...
March 10, 2018: Nucleic Acids Research
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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