Vs. BCR-ABL-Positive Cells to Interferon Alpha
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Activated Peripheral-Blood-Derived Mononuclear Cells
Transcription factor expression in lipopolysaccharide- activated peripheral-blood-derived mononuclear cells Jared C. Roach*†, Kelly D. Smith*‡, Katie L. Strobe*, Stephanie M. Nissen*, Christian D. Haudenschild§, Daixing Zhou§, Thomas J. Vasicek¶, G. A. Heldʈ, Gustavo A. Stolovitzkyʈ, Leroy E. Hood*†, and Alan Aderem* *Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; ‡Department of Pathology, University of Washington, Seattle, WA 98195; §Illumina, 25861 Industrial Boulevard, Hayward, CA 94545; ¶Medtronic, 710 Medtronic Parkway, Minneapolis, MN 55432; and ʈIBM Computational Biology Center, P.O. Box 218, Yorktown Heights, NY 10598 Contributed by Leroy E. Hood, August 21, 2007 (sent for review January 7, 2007) Transcription factors play a key role in integrating and modulating system. In this model system, we activated peripheral-blood-derived biological information. In this study, we comprehensively measured mononuclear cells, which can be loosely termed ‘‘macrophages,’’ the changing abundances of mRNAs over a time course of activation with lipopolysaccharide (LPS). We focused on the precise mea- of human peripheral-blood-derived mononuclear cells (‘‘macro- surement of mRNA concentrations. There is currently no high- phages’’) with lipopolysaccharide. Global and dynamic analysis of throughput technology that can precisely and sensitively measure all transcription factors in response to a physiological stimulus has yet to mRNAs in a system, although such technologies are likely to be be achieved in a human system, and our efforts significantly available in the near future. To demonstrate the potential utility of advanced this goal. We used multiple global high-throughput tech- such technologies, and to motivate their development and encour- nologies for measuring mRNA levels, including massively parallel age their use, we produced data from a combination of two distinct signature sequencing and GeneChip microarrays. -
Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells Carola E
Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells Carola E. Dehler, Katherine Lester, Giulia Della Pelle, Luc Jouneau, Armel Houel, Catherine Collins, Tatiana Dovgan, This information is current as Radek Machat, Jun Zou, Pierre Boudinot, Samuel A. M. of September 26, 2021. Martin and Bertrand Collet J Immunol published online 29 May 2019 http://www.jimmunol.org/content/early/2019/05/28/jimmun ol.1801376 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/05/28/jimmunol.180137 Material 6.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published May 29, 2019, doi:10.4049/jimmunol.1801376 The Journal of Immunology Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells Carola E. Dehler,* Katherine Lester,† Giulia Della Pelle,‡ Luc Jouneau,‡ Armel Houel,‡ Catherine Collins,† Tatiana Dovgan,*,† Radek Machat,‡,1 Jun Zou,*,2 Pierre Boudinot,‡ Samuel A. -
A Molecular Switch from STAT2-IRF9 to ISGF3 Underlies Interferon-Induced Gene Transcription
ARTICLE https://doi.org/10.1038/s41467-019-10970-y OPEN A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription Ekaterini Platanitis 1, Duygu Demiroz1,5, Anja Schneller1,5, Katrin Fischer1, Christophe Capelle1, Markus Hartl 1, Thomas Gossenreiter 1, Mathias Müller2, Maria Novatchkova3,4 & Thomas Decker 1 Cells maintain the balance between homeostasis and inflammation by adapting and inte- grating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our 1234567890():,; understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. Here, we use an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and IFN-γ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA. 1 Max Perutz Labs (MPL), University of Vienna, Vienna 1030, Austria. 2 Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna 1210, Austria. 3 Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna 1030, Austria. 4 Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna 1030, Austria. -
Inactivation of Type I IFN Jak-STAT Pathway in EBV Latency
Ning S and Wang L, J Cancer Biol Treat 2016, 3: 009 DOI: 10.24966/CBT-7546/100009 HSOA Journal of Cancer Biology and Treatment Research Article defense system, among which IRF7 is the “master” regulator of type I Inactivation of Type I IFN Interferon (IFN-I) response to pathogenic infection [4]. Robust IFN-I response during infection requires a positive feedback loop between Jak-STAT Pathway in EBV IRF7 and IFN-I [5-6]. Aberrant production of IFN-I, however, is Latency associated with autoimmune disorders and malignancies [7-9]. Thus, tight regulation of IRF7 is important in balancing the appropriate Shunbin Ning and Ling Wang* immune response to clear invading pathogens while preventing Department of Internal Medicine, Center of Excellence for Inflammation, immune-mediated pathogenesis [10]. Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, USA IFNs exert their functions through induction of IFN-Stimulated Genes (ISGs) via Jak-STAT pathways [11-13]. The IFN-I Jak-STAT pathway comprises of IFNAR1/2, Jak1, Tyk2, STAT1/2, and IRF9 [14]. Following IFN-I binding to IFNARs, signaling via protein kinases leads to tyrosine phosphorylation and activation of IFNAR1 Abstract at Y466 [15], Tyk2(Y1054/Y1055) and Jak1(Y1034/Y1035), and then to that Epstein-Barr Virus (EBV) latent infection is associated with a of STAT1(Y701) and STAT2(Y690 and S287) [16]. The phosphorylated variety of lymphomas and carcinomas. Interferon (IFN) Regulatory STAT1/2 then dimerize and associate with IRF9 to form a complex Factors (IRFs) are a family of transcription factors, among which termed interferon-stimulated gene factor 3 (ISGF3). -
Partner-Regulated Interaction of IFN Regulatory Factor 8 with Chromatin Visualized in Live Macrophages
Partner-regulated interaction of IFN regulatory factor 8 with chromatin visualized in live macrophages Leopoldo Laricchia-Robbio*, Tomohiko Tamura*, Tatiana Karpova†, Brian L. Sprague†, James G. McNally†, and Keiko Ozato*‡ *Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2753; and †Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055 Edited by Laurie H. Glimcher, Harvard School of Public Health, Boston, MA, and approved August 18, 2005 (received for review May 17, 2005) IFN regulatory factor (IRF) 8 is a transcription factor that directs protein–protein interactions on fluorescence recovery have not macrophage differentiation. By fluorescence recovery after pho- been extensively studied. Moreover, many FRAP studies so far tobleaching, we visualized the movement of IRF8-GFP in differen- reported are qualitative, lacking quantitative insight into the tiating macrophages. Recovery data fitted to mathematical models chromatin-binding events. More recent efforts to fit FRAP data revealed two binding states for IRF8. The majority of IRF8 was to mathematical models begin to provide a clearer knowledge on highly mobile and transiently interacted with chromatin, whereas the property of FRAP mobility (16, 17). a small fraction of IRF8 bound to chromatin more stably. IRF8 IRF8, a member of the IFN regulatory factor (IRF) family, is mutants that did not stimulate macrophage differentiation a key factor that guides the development of macrophages (18). showed a faster recovery, revealing little interaction with chro- We previously established an in vitro model system where matin. A macrophage activation signal by IFN-␥͞LPS led to a global IRF8Ϫ/Ϫ myeloid progenitor cells called Tot2 differentiate into slowdown of IRF8 movement, leading to increased chromatin macrophages upon IRF8 introduction (19). -
An Immunoevasive Strategy Through Clinically-Relevant Pan-Cancer Genomic and Transcriptomic Alterations of JAK-STAT Signaling Components
bioRxiv preprint doi: https://doi.org/10.1101/576645; this version posted March 14, 2019. 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-NC-ND 4.0 International license. An immunoevasive strategy through clinically-relevant pan-cancer genomic and transcriptomic alterations of JAK-STAT signaling components Wai Hoong Chang1 and Alvina G. Lai1, 1Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford, OX3 7FZ, United Kingdom Since its discovery almost three decades ago, the Janus ki- Although cytokines are responsible for inflammation in nase (JAK)-signal transducer and activator of transcription cancer, spontaneous eradication of tumors by endoge- (STAT) pathway has paved the road for understanding inflam- nous immune processes rarely occurs. Moreover, the matory and immunity processes related to a wide range of hu- dynamic interaction between tumor cells and host immu- man pathologies including cancer. Several studies have demon- nity shields tumors from immunological ablation, which strated the importance of JAK-STAT pathway components in overall limits the efficacy of immunotherapy in the clinic. regulating tumor initiation and metastatic progression, yet, the extent of how genetic alterations influence patient outcome is far from being understood. Focusing on 133 genes involved in Cytokines can be pro- or anti-inflammatory and are inter- JAK-STAT signaling, we found that copy number alterations dependent on each other’s function to maintain immune underpin transcriptional dysregulation that differs within and homeostasis(3). -
Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies Jinjong Myoung1, Shin-Ae Lee2, and Hye-Ra Lee3*
J. Microbiol. Biotechnol. (2019), 29(12), 1873–1881 https://doi.org/10.4014/jmb.1910.10004 Research Article Review jmb Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies Jinjong Myoung1, Shin-Ae Lee2, and Hye-Ra Lee3* 1Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, College of Natural Science, Jeonbuk National University, Jeonju 54531, Republic of Korea 2Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA 3Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea Received: October 8, 2019 Revised: October 8, 2019 The innate immune response serves as a first-line-of-defense mechanism for a host against Accepted: October 24, 2019 viral infection. Viruses must therefore subvert this anti-viral response in order to establish an First published online: efficient life cycle. In line with this fact, Kaposi’s sarcoma-associated herpesvirus (KSHV) October 25, 2019 encodes numerous genes that function as immunomodulatory proteins to antagonize the host *Corresponding author immune system. One such mechanism through which KSHV evades the host immunity is by Phone: +82-44-860-1831 encoding a viral homolog of cellular interferon (IFN) regulatory factors (IRFs), known as Fax: +82-44-860-1598 E-mail: [email protected] vIRFs. Herein, we summarize recent advances in the study of the immunomodulatory strategies of KSHV vIRFs and their effects on KSHV-associated pathogenesis. pISSN 1017-7825, eISSN 1738-8872 Copyright© 2019 by Keywords: KSHV, viral interferon regulatory factor, immune evasion strategy, PRR-mediated The Korean Society for Microbiology signaling pathway, apoptosis pathway and Biotechnology Introduction various transcription factors. -
Herpes Simplex Virus 1 Targets IRF7 Via ICP0 to Limit Type I IFN Induction David Shahnazaryan1,2, Rana Khalil3, Claire Wynne4, Caroline A
www.nature.com/scientificreports OPEN Herpes simplex virus 1 targets IRF7 via ICP0 to limit type I IFN induction David Shahnazaryan1,2, Rana Khalil3, Claire Wynne4, Caroline A. Jeferies5,6, Joan Ní Gabhann‑Dromgoole1,3,6* & Conor C. Murphy1,2,6 Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV‑1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear flm, where it encounters a multi‑pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti‑viral and pro‑infammatory cytokines. However, given that HSV‑1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual’s lifetime, there is signifcant interest in understanding the mechanisms employed by HSV‑1 to downregulate the anti‑viral type I interferon (IFN) mediated immune responses. This study aimed to investigate the interactions between infected cell protein (ICP)0 and key elements of the IFN pathway to identify possible novel targets that contribute to viral immune evasion. Reporter gene assays demonstrated the ability of ICP0 to inhibit type I IFN activity downstream of pathogen recognition receptors (PRRs) which are known to be involved in host antiviral defences. Further experiments identifed interferon regulatory factor (IRF)7, a driver of type I IFN, as a potential target for ICP0. These fndings increase our understanding of the pathogenesis of HSK and suggest IRF7 as a potential therapeutic target. Herpes simplex keratitis (HSK) is the commonest cause of infectious corneal blindness in the western world1. Tere are over 500,000 afected individuals in the United States (US) alone2. -
Role of Perforin-2 in Regulating Type I Interferon Signaling
https://www.scientificarchives.com/journal/journal-of-cellular-immunology Journal of Cellular Immunology Review Article Role of Perforin-2 in Regulating Type I Interferon Signaling Gregory V Plano, Noula Shembade* Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center Miller School of Medicine, University of Miami, Miami, FL 33136, USA *Correspondence should be addressed to Noula Shembade; [email protected] Received date: November 21, 2020, Accepted date: February 02, 2021 Copyright: © 2021 Plano G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Sepsis is a systemic inflammatory response caused by a harmful host immune reaction that is activated in response to microbial infections. Infection-induced type I interferons (IFNs) play critical roles during septic shock. Type I IFNs initiate their biological effects by binding to their transmembrane interferon receptors and initiating the phosphorylation and activation of tyrosine kinases TYK2 and JAK1, which promote phosphorylation and activation of STAT molecules. Type I IFN-induced activation of JAK/STAT pathways is a complex process and not well understood. Improper regulation of type I IFN responses can lead to the development of infectious and inflammation-related diseases, including septic shock, autoimmune diseases, and inflammatory syndromes. This review is mainly focused on the possible mechanistic roles of the transmembrane Perforin-2 molecule in the regulation of type I IFN- induced signaling. Keywords: JAK/STAT, Interferons, TYK2, STATs, Perforin-2, IFNAR1, IFNAR2 and Signaling Introduction and activator of transcription 2), respectively, under normal physiological conditions [4,5]. -
Transcription Factor IRF8 Directs a Silencing Programme for TH17 Cell Differentiation
ARTICLE Received 17 Aug 2010 | Accepted 13 Apr 2011 | Published 17 May 2011 DOI: 10.1038/ncomms1311 Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation Xinshou Ouyang1, Ruihua Zhang1, Jianjun Yang1, Qingshan Li1, Lihui Qin2, Chen Zhu3, Jianguo Liu4, Huan Ning4, Min Sun Shin5, Monica Gupta6, Chen-Feng Qi5, John Cijiang He1, Sergio A. Lira1, Herbert C. Morse III5, Keiko Ozato6, Lloyd Mayer1 & Huabao Xiong1 TH17 cells are recognized as a unique subset of T helper cells that have critical roles in the pathogenesis of autoimmunity and tissue inflammation. Although OR Rγt is necessary for the generation of TH17 cells, the molecular mechanisms underlying the functional diversity of TH17 cells are not fully understood. Here we show that a member of interferon regulatory factor (IRF) family of transcription factors, IRF8, has a critical role in silencing TH17-cell differentiation. Mice with a conventional knockout, as well as a T cell-specific deletion, of the Irf8 gene exhibited more efficient TH17 cells. Indeed, studies of an experimental model of colitis showed that IRF8 deficiency resulted in more severe inflammation with an enhanced TH17 phenotype. IRF8 was induced steadily and inhibited TH17-cell differentiation during TH17 lineage commitment at least in part through its physical interaction with RORγt. These findings define IRF8 as a novel intrinsic transcriptional inhibitor of TH17-cell differentiation. 1 Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 10029, USA. 2 Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA. -
Identification of Differentially Expressed Genes in Human Breast
www.impactjournals.com/oncotarget/ Oncotarget, 2018, Vol. 9, (No. 2), pp: 2475-2501 Research Paper Identification of differentially expressed genes in human breast cancer cells induced by 4-hydroxyltamoxifen and elucidation of their pathophysiological relevance and mechanisms Qi Fang1, Shuang Yao2, Guanghua Luo2 and Xiaoying Zhang2 1Department of Breast Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China 2Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China Correspondence to: Xiaoying Zhang, email: [email protected] Guanghua Luo, email: [email protected] Keywords: breast cancer; MCF-7; 4-hydroxyl tamoxifen; STAT1; STAT2 Received: June 05, 2017 Accepted: December 13, 2017 Published: December 20, 2017 Copyright: Fang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT While tamoxifen (TAM) is used for treating estrogen receptor (ER)a-positive breast cancer patients, its anti-breast cancer mechanisms are not completely elucidated. This study aimed to examine effects of 4-hydroxyltamoxifen (4-OH- TAM) on ER-positive (ER+) breast cancer MCF-7 cell growth and gene expression profiles. MCF-7 cell growth was inhibited by 4-OH-TAM dose-dependently with IC50 of 29 μM. 332 genes were up-regulated while 320 genes were down-regulated. The mRNA levels of up-regulated genes including STAT1, STAT2, EIF2AK2, TGM2, DDX58, PARP9, SASH1, RBL2 and USP18 as well as down-regulated genes including CCDN1, S100A9, S100A8, ANXA1 and PGR were confirmed by quantitative real-time PCR (qRT- PCR). -
A Dual Cis-Regulatory Code Links IRF8 to Constitutive and Inducible Gene Expression in Macrophages
Downloaded from genesdev.cshlp.org on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages Alessandra Mancino,1,3 Alberto Termanini,1,3 Iros Barozzi,1 Serena Ghisletti,1 Renato Ostuni,1 Elena Prosperini,1 Keiko Ozato,2 and Gioacchino Natoli1 1Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy; 2Laboratory of Molecular Growth Regulation, Genomics of Differentiation Program, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland 20892, USA The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8–PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF–AP-1 sites, which were not premarked by PU.1 and did not contribute to the basal IRF8 cistrome.