DOCSLIB.ORG

Determination of Transforming Growth Factor-Β Signaling Targets in Activated T Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Determination of Transforming Growth Factor-Β Signaling Targets in Activated T Cells Loyola University Chicago Loyola eCommons Dissertations Theses and Dissertations 2019 Determination of Transforming Growth Factor-β Signaling Targets in Activated T Cells Ramiah Jacks Follow this and additional works at: https://ecommons.luc.edu/luc_diss Part of the Immunology of Infectious Disease Commons Recommended Citation Jacks, Ramiah, "Determination of Transforming Growth Factor-β Signaling Targets in Activated T Cells" (2019). Dissertations. 3341. https://ecommons.luc.edu/luc_diss/3341 This Dissertation is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Dissertations by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 2019 Ramiah Jacks LOYOLA UNIVERSITY CHICAGO DETERMINATION OF TRANSFORMING GROWTH FACTOR-β TYPE I RECEPTOR (TGF-βRI) SIGNALING TARGETS IN ACTIVATED T CELLS A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY PROGRAM IN MICROBIOLOGY AND IMMUNOLOGY BY RAMIAH D. JACKS CHICAGO, ILLINOIS AUGUST 2019 ACKNOWLEDGMENTS I would like to first acknowledgment my parents, Greg and Regina Jacks, for their love, encouragement, commitment to my success, and, most importantly, their sacrifices. I will be forever grateful for their unwavering dedication to ensuring that their children have the education and resources required to achieve anything that we desire. I am extremely appreciative of the opportunities afforded to me because of the hard work, strength and perseverance of my parents, extended family members and ancestors. I recognize that I am living the dreams of my ancestors and, inspired by their efforts, I strive to create an even better future for the next generation. I also would like to thank my sister Rakeva, brother Greg, and my boyfriend Joseph for their unconditional love and support, as well as regular therapeutic fun and laughs. I am also extremely appreciative for the leadership and mentorship of Dr. Makio Iwashima. Makio was instrumental in the development of my ‘scientific mind’. He is an incredible scientist and taught me that the drivers of science are data, even if they do not support your hypotheses. We’ve had regular enriching conversations and meetings about my data and his feedback was invaluable for my development as an immunologist. I’ve thoroughly enjoyed my time in Makio’s lab and I look forward to continue to collaborate with him the in future. I must also thank my friends/labmates in the Iwashima lab, both old and new. Not only did we have great conversations about the directions of our projects and how to improve presentations, we also had a lot of fun together. We were very collaborative iii and had no problem helping each other with whatever was needed, in the lab or in our personal lives. Their support and friendship are things that I will cherish forever. Finally, I cannot thank my committee enough. Drs. Phong Le, Katherine Knight, Clodia Osipo and Jose Guevara-Piñto always provided critical and constructive feedback that kept my project moving forward in meaningful ways. Their mentorship also allowed me to become a better scientist and communicator. In addition, this work would not be possible without: funding support from the T32 Immunology Training Grant to Dr. Knight; funding support from the Predoctoral Ruth L. Kirchstein National Research Service F31 Diversity Award from the from the National Institute of General Medical Sciences (NIGMS), the guidance and expertise of Pat Simms, Ashley Hess and Steven Kirk at the flow cytometry core; and the continued support and encouragement from the students, faculty, and staff of the Department of Microbiology and Immunology. iv TABLE OF CONTENTS ACKNOWLEDGEMENTS ................................................................................................ iii LIST OF FIGURES ......................................................................................................... viii ABSTRACT ...................................................................................................................... x CHAPTER ONE: REVIEW OF LITERATURE .................................................................. 1 T lymphopoiesis ............................................................................................................ 1 Positive and Negative selection .................................................................................... 4 T cell Subsets ................................................................................................................ 6 CD4+ T cell Subsets ................................................................................................... 6 CD8+ T cell Subsets ................................................................................................. 11 Perinatal vs Adult T cells……………………………… .................................................. 11 Transforming Growth Factor-β (TGF-β) ...................................................................... 13 Processing of TGF-β ............................................................................................... 14 Activation of Latent TGF-β ....................................................................................... 16 TGF-β Signal Propagation ........................................................................................... 19 Canonical TGF-β Signaling ...................................................................................... 22 Non-canonical TGF-β Signaling ............................................................................... 24 TGF-β Signaling in T cells ........................................................................................... 25 TGF-β Signaling in T cell Differentiation ................................................................... 25 TGF-β Signaling in T cell Suppression ..................................................................... 29 c-Jun Amino-Terminal Kinase (JNK) Activation in T cells………… ............................. 31 Upstream Kinases in JNK Activation ........................................................................ 31 Adaptor Molecules, CARMA1 and BCL10, in JNK Activation .................................. 34 JNK Substrates: The Jun Family of Transcription Factors .......................................... 39 c-Jun ......................................................................................................................... 40 Jun B ........................................................................................................................ 41 Jun D ........................................................................................................................ 42 The Function of JNK1 and JNK2 in T cells .................................................................. 43 JNK1 and JNK2 Signaling in T cell Activation .......................................................... 43 JNK1 and JNK2 Signaling in T cell Differentiation ................................................... 45 JNK1 and JNK2 Signaling in T cell Apoptosis .......................................................... 46 Purpose of Dissertation ............................................................................................... 47 CHAPTER TWO: MATERIALS AND METHODS ........................................................... 49 Cell Preparation and Reagents ................................................................................... 49 Phenotype Analysis and Cytokine Profile of Naïve CD4+ T cells ................................ 50 Th1 and Th2 Differentiation Assays ............................................................................ 51 Generation of a TGF-βRI Deficient Jurkat T cell Line using CRISPR/cas9 Genome Editing ........................................................................................................ 51 Stimulation of the TGF-βRI Deficient Jurkat T cell Line ............................................. 52 Stimulation of the Primary Human 1383I TCR T cell Line ........................................... 53 Western Blot Analysis ................................................................................................. 54 Flow Cytometry............................................................................................................ 54 v Reporter Assays in the TGF-βRI Deficient Jurkat T cell Line and Primary Human T cells........................................................................................................... 55 RNA Sequence Analysis of the TGF-βRI Deficient Jurkat T cell Line ......................... 56 Activation of Primary Mouse T cells ............................................................................ 57 Statistical Analysis ...................................................................................................... 57 CHAPTER THREE: RESULTS ....................................................................................... 58 SECTION 1: Characterization of Naïve CD4+ T cells from Umbilical Cord Blood vs Peripheral Adult Blood ............................................................................ 58 CD26 is Highly Expressed by Naïve CD4+ T cells from Umbilical Cord Blood ..................................................................................................................... 60 IL-7 Induced
Load more

Recommended publications
  • Análise Integrativa De Perfis Transcricionais De Pacientes Com
    UNIVERSIDADE DE SÃO PAULO FACULDADE DE MEDICINA DE RIBEIRÃO PRETO PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Ribeirão Preto – 2012 ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Tese apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Genética Orientador: Prof. Dr. Eduardo Antonio Donadi Co-orientador: Prof. Dr. Geraldo A. S. Passos Ribeirão Preto – 2012 AUTORIZO A REPRODUÇÃO E DIVULGAÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE. FICHA CATALOGRÁFICA Evangelista, Adriane Feijó Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. Ribeirão Preto, 2012 192p. Tese de Doutorado apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Área de Concentração: Genética. Orientador: Donadi, Eduardo Antonio Co-orientador: Passos, Geraldo A. 1. Expressão gênica – microarrays 2. Análise bioinformática por module maps 3. Diabetes mellitus tipo 1 4. Diabetes mellitus tipo 2 5. Diabetes mellitus gestacional FOLHA DE APROVAÇÃO ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas.
    [Show full text]
  • Characteristics of B Cell-Associated Gene Expression in Patients With
    MOLECULAR MEDICINE REPORTS 13: 4113-4121, 2016 Characteristics of B cell-associated gene expression in patients with coronary artery disease WENWEN YAN*, HAOMING SONG*, JINFA JIANG, WENJUN XU, ZHU GONG, QIANGLIN DUAN, CHUANGRONG LI, YUAN XIE and LEMIN WANG Department of Internal Medicine, Division of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China Received May 19, 2015; Accepted February 12, 2016 DOI: 10.3892/mmr.2016.5029 Abstract. The current study aimed to identify differentially with the two other groups. Additionally the gene expression expressed B cell-associated genes in peripheral blood mono- levels of B cell regulatory genes were measured. In patients nuclear cells and observe the changes in B cell activation at with AMI, CR1, LILRB2, LILRB3 and VAV1 mRNA expres- different stages of coronary artery disease. Groups of patients sion levels were statistically increased, whereas, CS1 and IL4I1 with acute myocardial infarction (AMI) and stable angina (SA), mRNAs were significantly reduced compared with the SA and as well as healthy volunteers, were recruited into the study control groups. There was no statistically significant difference (n=20 per group). Whole human genome microarray analysis in B cell-associated gene expression levels between patients was performed to examine the expression of B cell-associated with SA and the control group. The present study identified the genes among these three groups. The mRNA expression levels downregulation of genes associated with BCRs, B2 cells and of 60 genes associated with B cell activity and regulation were B cell regulators in patients with AMI, indicating a weakened measured using reverse transcription-quantitative polymerase T cell-B cell interaction and reduced B2 cell activation during chain reaction.
    [Show full text]
  • Molecular and Epigenetic Features of Melanomas and Tumor Immune
    Seremet et al. J Transl Med (2016) 14:232 DOI 10.1186/s12967-016-0990-x Journal of Translational Medicine RESEARCH Open Access Molecular and epigenetic features of melanomas and tumor immune microenvironment linked to durable remission to ipilimumab‑based immunotherapy in metastatic patients Teofila Seremet1,3*† , Alexander Koch2†, Yanina Jansen1, Max Schreuer1, Sofie Wilgenhof1, Véronique Del Marmol3, Danielle Liènard3, Kris Thielemans4, Kelly Schats5, Mark Kockx5, Wim Van Criekinge2, Pierre G. Coulie6, Tim De Meyer2, Nicolas van Baren6,7 and Bart Neyns1 Abstract Background: Ipilimumab (Ipi) improves the survival of advanced melanoma patients with an incremental long-term benefit in 10–15 % of patients. A tumor signature that correlates with this survival benefit could help optimizing indi- vidualized treatment strategies. Methods: Freshly frozen melanoma metastases were collected from patients treated with either Ipi alone (n: 7) or Ipi combined with a dendritic cell vaccine (TriMixDC-MEL) (n: 11). Samples were profiled by immunohistochemistry (IHC), whole transcriptome (RNA-seq) and methyl-DNA sequencing (MBD-seq). Results: Patients were divided in two groups according to clinical evolution: durable benefit (DB; 5 patients) and no clinical benefit (NB; 13 patients). 20 metastases were profiled by IHC and 12 were profiled by RNA- and MBD-seq. 325 genes were identified as differentially expressed between DB and NB. Many of these genes reflected a humoral and cellular immune response. MBD-seq revealed differences between DB and NB patients in the methylation of genes linked to nervous system development and neuron differentiation. DB tumors were more infiltrated by CD8+ and PD-L1+ cells than NB tumors.
    [Show full text]
  • Identifying Loci Under Positive Selection in Complex Population Histories
    Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Method Identifying loci under positive selection in complex population histories Alba Refoyo-Martínez,1 Rute R. da Fonseca,2 Katrín Halldórsdóttir,3 Einar Árnason,3,4 Thomas Mailund,5 and Fernando Racimo1 1Lundbeck GeoGenetics Centre, The Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 1350, Denmark; 2Centre for Macroecology, Evolution and Climate, The Globe Institute, Faculty of Health and Medical Sciences, University of Copenhagen, Copehnagen 2100, Denmark; 3Faculty of Life and Environmental Sciences, University of Iceland, Reykjavík 107, Iceland; 4Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA; 5Bioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark Detailed modeling of a species’ history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method—called graph-aware retrieval of selective sweeps (GRoSS)—has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish, and human population genomic data containing panels of multiple populations related in complex ways.
    [Show full text]
  • Epigenetic Regulation of Developmental Expression of Cyp2d Genes in Mouse Liver
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Acta Pharmaceutica Sinica B 2012;2(2):146–158 Institute of Materia Medica, Chinese Academy of Medical Sciences Chinese Pharmaceutical Association Acta Pharmaceutica Sinica B www.elsevier.com/locate/apsb www.sciencedirect.com ORIGINAL ARTICLE Epigenetic regulation of developmental expression of Cyp2d genes in mouse liver Ye Lia, Xiao-bo Zhongb,n aDepartment of Pharmacology, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China bDepartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA Received 28 November 2011; revised 26 December 2011; accepted 10 January 2012 KEY WORDS Abstract CYP2D6 expression in liver is age-dependent. Because epigenetic mechanisms, such as DNA methylation and histone modifications, modulate age-related gene expression during develop- Cyp2d; ment, and are highly conserved among species, the current study examined the epigenetic regulation of DNA methylation; age-related expression of the Cyp2d genes in mouse liver. DNA methylation (DNAme), histone 3 Histone methylation; lysine 4 dimethylation (H3K4me2), and histone 3 lysine 27 trimethylation (H3K27me3) was Liver development established by ChIP-on-chip tiling microarrays from mouse livers at prenatal, neonatal, and adult stages. Levels of DNAme, H3K4me2, and H3K27me3 were analyzed in a genomic region containing the Cyp2d clustering genes and their surrounding genes. Gradually increased expression levels of the Cyp2d9, Cyp2d10, Cyp2d22,andCyp2d26 genes from prenatal, through neonatal, to adult are associated with gradually increased levels of H3K4me2 in the nucleosomes associated with these genes. Gene expression patterns during liver development in several Cyp2d surrounding genes, such as Srebf2, Sept3, Ndufa6, Tcf2, Nfam1,andCyb5r3, could be also explained by changes of DNA methylation, H3K4me2, or H3K27me3 in those genes.
    [Show full text]
  • Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
    Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo
    [Show full text]
  • Systematic Elucidation of Neuron-Astrocyte Interaction in Models of Amyotrophic Lateral Sclerosis Using Multi-Modal Integrated Bioinformatics Workflow
    ARTICLE https://doi.org/10.1038/s41467-020-19177-y OPEN Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow Vartika Mishra et al.# 1234567890():,; Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. Herein, we propose an approach for the Systematic Elucidation and Assessment of Regulatory Cell-to-cell Interaction Net- works (SEARCHIN) to identify ligand-mediated interactions between distinct cellular com- partments. To test this approach, we selected a model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs) by an unknown mechanism. Our integrative analysis that combines proteomics and regulatory network analysis infers the interaction between astrocyte-released amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred deleterious role of APP and DR6 is confirmed in vitro in models of ALS. Moreover, the DR6 knockdown in MNs of transgenic mutSOD1 mice attenuates the ALS-like phenotype. Our results support the usefulness of integrative, systems biology approach to gain insights into complex neurobiological disease processes as in ALS and posit that the proposed methodology is not restricted to this biological context and could be used in a variety of other non-cell-autonomous communication
    [Show full text]
  • Chromothripsis and Ring Chromosome 22: a Paradigm of Genomic
    JMG Online First, published on January 29, 2018 as 10.1136/jmedgenet-2017-105125 Genome-wide studies J Med Genet: first published as 10.1136/jmedgenet-2017-105125 on 29 January 2018. Downloaded from ORIGINAL ARTICLE Chromothripsis and ring chromosome 22: a paradigm of genomic complexity in the Phelan-McDermid syndrome (22q13 deletion syndrome) Nehir Kurtas,1 Filippo Arrigoni,2 Edoardo Errichiello,1 Claudio Zucca,3 Cristina Maghini,4 Maria Grazia D’Angelo,4 Silvana Beri,5 Roberto Giorda,5 Sara Bertuzzo,6 Massimo Delledonne,7 Luciano Xumerle,7 Marzia Rossato,7 Orsetta Zuffardi,1 Maria Clara Bonaglia6 ► Additional material is ABSTRact structural component of the glutamatergic post- published online only. To view Introduction Phelan-McDermid syndrome (PMS) synaptic density.6 Patients with PMS mainly exhibit please visit the journal online (http:// dx. doi. org/ 10. 1136/ is caused by SHANK3 haploinsufficiency. Its wide neurological and behavioural symptoms including jmedgenet- 2017- 105125). phenotypic variation is attributed partly to the type and hypotonia, intellectual disability (ID), impaired size of 22q13 genomic lesion (deletion, unbalanced language development (delayed or absent speech), 1 Department of Molecular translocation, ring chromosome), partly to additional behavioural features consistent with disorders of Medicine, University of Pavia, undefined factors. We investigated a child with severe the autistic spectrum and seizures. Pavia, Italy 2Neuroimaging Laboratory, global neurodevelopmental delay (NDD) compatible The penetrance and expressivity of these symp- Scientific Institute, IRCCS with her distal 22q13 deletion, complicated by bilateral toms may be variable, with different degrees of Eugenio Medea, Bosisio Parini, perisylvian polymicrogyria (BPP) and urticarial rashes, severity at different ages3 7–9 as well as congenital Italy 4 5 3 unreported in PMS.
    [Show full text]
  • Overexpression of an Activated REL Mutant Enhances the Transformed State of the Human B-Lymphoma BJAB Cell Line and Alters Its Gene Expression Profile
    Oncogene (2009) 28, 2100–2111 & 2009 Macmillan Publishers Limited All rights reserved 0950-9232/09 $32.00 www.nature.com/onc ORIGINAL ARTICLE Overexpression of an activated REL mutant enhances the transformed state of the human B-lymphoma BJAB cell line and alters its gene expression profile M Chin1, M Herscovitch1, N Zhang, DJ Waxman and TD Gilmore Department of Biology, Boston University, Boston, MA, USA The human REL proto-oncogene encodes a transcription factor. Misregulated REL is associated with B-cell factor in the nuclear factor (NF)-kB family. Overexpres- malignancies in several ways (Gilmore et al., sion of REL is acutely transforming in chicken lymphoid 2004). Overexpression of REL protein can transform cells, but has not been shown to transform any mammalian chicken lymphoid cells in vitro. Additionally, the lymphoid cell type. In this report, we show that over- REL locus is amplified in several types of human expression of a highly transforming mutant of REL B-cell lymphoma, including diffuse large B-cell lympho- (RELDTAD1) increases the oncogenic properties of the ma (DLBCL), follicular and primary mediastinal human B-cell lymphoma BJAB cell line, as shown by lymphomas. Moreover, REL mRNA is highly expressed increased colony formation in soft agar, tumor formation in de novo DLBCLs, and this elevated expression in SCID (severe combined immunodeficient) mice, and correlates with increased expression of many adhesion. BJAB-RELDTAD1 cells also show decreased putative REL target genes (Rhodes et al., 2005). activation of caspase in response to doxorubicin. BJAB- Nevertheless, REL has not been shown to be oncogenic RELDTAD1 cells have increased levels of active nuclear in any mammalian B-cell system, either in vitro REL protein as determined by immunofluorescence, or in vivo.
    [Show full text]
  • A Framework to Identify Contributing Genes in Patients with Phelan-Mcdermid Syndrome
    www.nature.com/npjgenmed Corrected: Author Correction ARTICLE OPEN A framework to identify contributing genes in patients with Phelan-McDermid syndrome Anne-Claude Tabet 1,2,3,4, Thomas Rolland2,3,4, Marie Ducloy2,3,4, Jonathan Lévy1, Julien Buratti2,3,4, Alexandre Mathieu2,3,4, Damien Haye1, Laurence Perrin1, Céline Dupont 1, Sandrine Passemard1, Yline Capri1, Alain Verloes1, Séverine Drunat1, Boris Keren5, Cyril Mignot6, Isabelle Marey7, Aurélia Jacquette7, Sandra Whalen7, Eva Pipiras8, Brigitte Benzacken8, Sandra Chantot-Bastaraud9, Alexandra Afenjar10, Delphine Héron10, Cédric Le Caignec11, Claire Beneteau11, Olivier Pichon11, Bertrand Isidor11, Albert David11, Laila El Khattabi12, Stephan Kemeny13, Laetitia Gouas13, Philippe Vago13, Anne-Laure Mosca-Boidron14, Laurence Faivre15, Chantal Missirian16, Nicole Philip16, Damien Sanlaville17, Patrick Edery18, Véronique Satre19, Charles Coutton19, Françoise Devillard19, Klaus Dieterich20, Marie-Laure Vuillaume21, Caroline Rooryck21, Didier Lacombe21, Lucile Pinson22, Vincent Gatinois22, Jacques Puechberty22, Jean Chiesa23, James Lespinasse24, Christèle Dubourg25, Chloé Quelin25, Mélanie Fradin25, Hubert Journel26, Annick Toutain27, Dominique Martin28, Abdelamdjid Benmansour1, Claire S. Leblond2,3,4, Roberto Toro2,3,4, Frédérique Amsellem29, Richard Delorme2,3,4,29 and Thomas Bourgeron2,3,4 Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability (ID), absent or delayed speech, and autism spectrum disorders (ASD). It results from a deletion of the distal part of chromosome 22q13 that in most cases includes the SHANK3 gene. SHANK3 is considered a major gene for PMS, but the factors that modulate the severity of the syndrome remain largely unknown. In this study, we investigated 85 patients with different 22q13 rearrangements (78 deletions and 7 duplications).
    [Show full text]
  • Peripheral Blood Gene Expression Profiles in Metabolic Syndrome, Coronary Artery Disease and Type 2 Diabetes
    Genes and Immunity (2011) 12, 341–351 & 2011 Macmillan Publishers Limited All rights reserved 1466-4879/11 www.nature.com/gene ORIGINAL ARTICLE Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes BL Grayson1, L Wang2 and TM Aune1,3 1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA and 3Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease (CAD), type 2 diabetes (T2D) and their precursor state, metabolic syndrome to those of control (CTRL) subjects and subjects with rheumatoid arthritis (RA). The gene expression profile of each metabolic state was distinguishable from CTRLs and correlated with other metabolic states more than with RA. Of note, subjects in the metabolic cohorts overexpressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-kB, were overexpressed in CAD whereas genes differentially expressed in T2D have key roles in T-cell activation and signaling. Reverse transcriptase PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and T2D. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.
    [Show full text]
  • 1 a Framework to Identify Modifier Genes in Patients With
    bioRxiv preprint doi: https://doi.org/10.1101/117978; this version posted March 18, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. A framework to identify modifier genes in patients with Phelan-McDermid syndrome Short running title: Mapping modifier genes in Phelan-McDermid Syndrome Anne-Claude Tabet1,2,3,4¶, Thomas Rolland2,3,4¶, Marie Ducloy2,3,4, Jonathan Lévy1, Julien Buratti2,3,4, Alexandre Mathieu2,3,4, Damien Haye1, Laurence Perrin1, Céline Dupont1, Sandrine Passemard1, Yline Capri1, Alain Verloes1, Séverine Drunat1, Boris Keren5, Cyril Mignot6, Isabelle Marey7, Aurélia Jacquette7, Sandra Whalen7, Eva Pipiras8, Brigitte Benzacken8, Sandra Chantot-Bastaraud9, Alexandra Afenjar10, Delphine Héron10, Cédric Le Caignec11, Claire Beneteau11, Olivier Pichon11, Bertrand Isidor11, Albert David11, Jean-Michel Dupont12, Stephan Kemeny13, Laetitia Gouas13, Philippe Vago13, Anne-Laure Mosca-Boidron14, Laurence Faivre15, Chantal Missirian16, Nicole Philip16, Damien Sanlaville17, Patrick Edery18, Véronique Satre19, Charles Coutton19, Françoise Devillard19, Klaus Dieterich20, Marie-Laure Vuillaume21, Caroline Rooryck21, Didier Lacombe21, Lucile Pinson22, Vincent Gatinois22, Jacques Puechberty22, Jean Chiesa23, James Lespinasse24, Christèle Dubourg25, Chloé Quelin25, Mélanie Fradin25, Hubert Journel26, Annick Toutain27, Dominique Martin28, Abdelamdjid Benmansour1,
    [Show full text]