DOCSLIB.ORG

Regulatory T Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulatory T Cells Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Protein high, This information is current as Foxp3-Expressing CD25 + and CD25− of September 29, 2021. Regulatory T Cells Masahiro Ono, Jun Shimizu, Yoshiki Miyachi and Shimon Sakaguchi Downloaded from J Immunol 2006; 176:4748-4756; ; doi: 10.4049/jimmunol.176.8.4748 http://www.jimmunol.org/content/176/8/4748 http://www.jimmunol.org/ References This article cites 51 articles, 27 of which you can access for free at: http://www.jimmunol.org/content/176/8/4748.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 29, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *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 © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Control of Autoimmune Myocarditis and Multiorgan Inflammation by Glucocorticoid-Induced TNF Receptor Family-Related Proteinhigh, Foxp3-Expressing CD25؉ and CD25؊ Regulatory T Cells1 Masahiro Ono,*† Jun Shimizu,‡ Yoshiki Miyachi,† and Shimon Sakaguchi2*§ Anomalies of naturally occurring CD4؉ regulatory T cells (Treg) cause severe autoimmune/inflammatory diseases in humans and rodents. The transcription factor Foxp3 is currently the most specific marker for natural CD4؉ Treg, but it would be useful if other Treg markers, particularly cell surface molecules, could be elucidated. We demonstrate in this study that the vast majority of Foxp3-expressing CD4؉ T cells (whether CD25؉ or CD25؊) show constitutive high-level expression of glucocorticoid-induced Downloaded from TNFR family-related gene/protein (GITR). Transfer of T cell or thymocyte suspensions depleted of GITRhigh cells produces in BALB/c nude mice a wider spectrum and more severe forms of autoimmune diseases than does transfer of similar cell suspensions depleted of CD25؉CD4؉ T cells only. Notably, mice that receive cells depleted of GITRhigh populations develop severe multiorgan inflammation that includes fatal autoimmune myocarditis resembling giant cell myocarditis in humans, accompanying high-titer anti-myosin autoantibodies. Similar transfer of GITRhigh-depleted cells from prediabetic NOD mice to NOD-SCID mice acceler- ates the development of diabetes and induces skeletal muscle myositis and other autoimmune/inflammatory diseases. We conclude http://www.jimmunol.org/ that GITRhigh, Foxp3-expressing natural Treg, containing both CD25؉ and CD25؊ cell populations, contribute to preventing a variety of autoimmune/inflammatory diseases, and depletion of these cells allows the activation of even weak or rare autoreactive T cells yielding widespread severe autoimmune disease. Diseases induced in this way include many which have been suspected of an autoimmune etiology in humans without much evidence. GITRhigh, Foxp3-expressing natural Treg represent a potential target for the treatment and prevention of these diseases. The Journal of Immunology, 2006, 176: 4748–4756. here is accumulating evidence that regulatory T cells type 1 diabetes (T1D) and thyroiditis), inflammatory bowel dis- (Treg),3 in particular naturally occurring CD25ϩCD4ϩ ease, and allergy (such as allergic dermatitis and food allergy) (4, T Treg, play crucial roles in the maintenance of immuno- 5). The disease is so severe that Ͼ80% of the patients, including by guest on September 29, 2021 logic self-tolerance and suppressive control of a variety of patho- those with a diabetes-protective HLA haplotype, develop T1D and logical and physiological immune responses (1–3). Depletion of other autoimmune diseases (5). The cause of IPEX is mutation of ϩ ϩ CD25 CD4 Treg, for example, elicits autoimmune disease in the gene FOXP3, which encodes the forkhead/winged-helix tran- multiple organs such as stomach and thyroid in otherwise normal scription factor Scurfin (5). CD25ϩCD4ϩ natural Treg in mice animals, provokes effective tumor immunity to autologous tumor specifically express Foxp3 (the murine ortholog of human cells, enhances immune responses to invading or cohabiting mi- FOXP3), and ectopic or transgenic expression of Foxp3 can con- crobes, and triggers allergic responses to innocuous environmental vert naive T cells to Treg that phenotypically and functionally substances. The best example of the role of natural Treg in humans ϩ ϩ resemble natural CD25 CD4 Treg (6–8). Foxp3-defective or is a fatal autoimmune/inflammatory disease called IPEX (immune ϩ ϩ -deficient mice fail to develop CD25 CD4 Treg, leading to the dysregulation, polyendocrinopathy, enteropathy, X-linked syn- occurrence of fatal inflammatory disease (7). Foxp3 thus appears drome), which accompanies severe autoimmune disease (such as to be a master control gene for the development and function of naturally occurring Treg, and is currently the most specific molec- *Department of Experimental Pathology, Institute for Frontier Medical Sciences, ular marker for this T cell subpopulation (6–9). A critical question, Kyoto University, Kyoto, Japan; †Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; ‡Tokyo Metropolitan Institute for Ger- then, in elucidating the cause and mechanism of human autoim- ontology, Itabashi-ku, Tokyo, Japan; and §Core Research for Evolutional Science and mune diseases is how FOXP3 deficiency causes such fatal auto- Technology, Japan Science and Technology Agency, Kawaguchi, Japan immune/inflammatory diseases, and whether anomaly of FOXP3- Received for publication December 12, 2005. Accepted for publication January 26, 2006. expressing Treg can be a cause of other human inflammatory The costs of publication of this article were defrayed in part by the payment of page diseases including those where etiology is unknown. charges. This article must therefore be hereby marked advertisement in accordance It has been shown that CD25, the IL-2R ␣-chain, is not only a with 18 U.S.C. Section 1734 solely to indicate this fact. useful molecular marker for natural CD4ϩ Treg but also an essen- 1 This work was supported by grants-in-aid from the Ministry of Education, Sports tial molecule for their development and function as an indispens- and Culture of Japan. able component of the high-affinity IL-2R. For example, IL-2-, 2 Address correspondence and reprint requests to Dr. Shimon Sakaguchi, Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, CD25-, or CD122 (IL-2R ␤-chain)-deficient mice develop fatal 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail address: autoimmune/inflammatory disease similar to Foxp3 deficiency [email protected] (10–12). Neutralization of circulating IL-2 for a limited period 3 Abbreviations used in this paper: Treg, regulatory T cell; IPEX, immune dysregu- ϩ ϩ lation, polyendocrinopathy, enteropathy, X-linked syndrome; T1D, type 1 diabetes; selectively reduces the number of CD25 CD4 Treg and elicits GITR, glucocorticoid-induced TNFR family-related protein; C, complement. autoimmune disease similar to the one produced by depletion of Copyright © 2006 by The American Association of Immunologists, Inc. 0022-1767/06/$02.00 The Journal of Immunology 4749 ϩ ϩ CD25 CD4 Treg (13). In contrast, there is accumulating evi- purified by the MACS system (Miltenyi Biotec), using biotinylated anti- dence for the existence of regulatory activity in the CD25ϪCD4ϩ CD4, anti-CD8, or anti-CD19, respectively, with PE-labeled streptavidin T cell population. For example, CD25ϪCD45RBlowCD4ϩ T cells and anti-PE microbeads. Other T cell subpopulations were prepared as Ϫ ϩ ϩ described previously (19). For assessing GITR expression on the residual in rodents and CD25 CD45RO CD4 T cells in humans contain cells after anti-GITR (DTA-1) or anti-CD25 (7D4)ϩC (complement)-treat- cells expressing Foxp3/FOXP3 at a low level (6, 9, 14). ment or C-treatment alone, they were incubated again with DTA-1 and CD25ϪCD4ϩ T cells bear an autoimmune-suppressive activity in 7D4, washed, and stained with rabbit polyclonal biotinylated anti-murine various animal models of autoimmune disease, although the activ- GITR Ab. ϩ ϩ ity is generally weaker than that of natural CD25 CD4 Treg Quantitation of mRNA expression by real-time RT-PCR (15–17). It must be determined then to what degree CD25ϪCD4ϩ Treg contribute to the maintenance of natural self-tolerance and Quantitation of Foxp3 and HPRT mRNA by real-time PCR was described previously (6). how severe the autoimmune diseases will be, in particular what spectrum of autoimmune/inflammatory disease will develop, when Histopathology ϩ Ϫ both CD25 and CD25 Foxp3-expressing Treg are depleted from Myocarditis and other autoimmune diseases were histologically evaluated the normal immune system. and graded as described previously (21–23). CD25ϩCD4ϩ Treg express GITR (glucocorticoid-induced TNFR family related gene/protein) at higher levels than other T Immunohistochemistry
Load more

Recommended publications
  • The Title of the Dissertation
    UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic
    [Show full text]
  • The Effects of Estrogen in Atrazine-Mediated Foxp3 Induction and Inhibition of Cd4+ T Effector Cells
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 2014 THE EFFECTS OF ESTROGEN IN ATRAZINE-MEDIATED FOXP3 INDUCTION AND INHIBITION OF CD4+ T EFFECTOR CELLS Tiffany Emmons The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Emmons, Tiffany, "THE EFFECTS OF ESTROGEN IN ATRAZINE-MEDIATED FOXP3 INDUCTION AND INHIBITION OF CD4+ T EFFECTOR CELLS" (2014). Graduate Student Theses, Dissertations, & Professional Papers. 4350. https://scholarworks.umt.edu/etd/4350 This Thesis is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. THE EFFECTS OF ESTROGEN IN ATRAZINE-MEDIATED FOXP3 INDUCTION AND INHIBITION OF CD4+ T EFFECTOR CELLS By TIFFANY ROSE EMMONS B.S. Biology, University of California, Merced, Merced, California, 2012 Thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Cellular, Molecular and Microbial Biology Option: Immunology The University of Montana Missoula, MT Official Graduation Date: July 2014 Approved by: J. B. Alexander Ross, Dean of The Graduate School Graduate School Dr. Scott Wetzel, Chair Division of Biological Sciences Dr. Stephen Lodmell Division of Biological Sciences Dr. David Shepherd Department of Biomedical and Pharmaceutical Sciences Emmons, Tiffany, M.S. Summer 2014 Biology The Effects of Estrogen in Atrazine-mediated Foxp3 Induction and Inhibition of CD4+ T effector Cells Atrazine (ATR) is a chlorotriazine herbicide that is heavily used in agricultural areas.
    [Show full text]
  • Contribution of T Cell-Mediated Immunity to the Resistance
    0022-202X/ 78/ 7006 0345$02.00/ 0 THE JOURNAL OF I NVESTIGATIVE DERMATOLOGY, 70:345-347, 1978 Vol. 70, No. 6 Copyright © 1978 by The Williams & Wilkins Co. Printed in U.S.A. Contribution ofT Cell-mediated Immunity to the Resistance to Staphylococcal Infection SHINGO TSUDA, M.D., YOICHIRO SASAI, M.D., KIKUO MINAMI, M.D., AND KIKUO NOMOTO, M.D. Department of Dermatology, Kurume University School of Medicine, Kurume, Japan, and Department of Immunology, Institute for Cancer Research, Kyushu University School of Medicine, Fuhuoha, Japan. Abscess formation in nude mice after subcutaneous -, DNase + and hemolysis of a type. The bacteria were cultured in a inoculation of Staphylococcus aureus (S. aureus) was meat infusion broth (distilled water 100 ml, meat extract obtained from more extensive and prolonged as compared with that in beef 5 gm, NaCl5 gm and NaHC03 0.5 gm) at 37°C for 24 hr, centrifuged phenotypically normallittermates. Abscess formation in at 3000 rpm for 30 min and resuspended in saline. Bacterial suspensions comparable to 1.7 x 107 colony-forming markedly by whole-body ir­ were adjusted to a dose nude mice was augmented units/ ml after estimation with a spectrophotometer at 580 nm (Hita­ radiation. Not only T cell-mediated immunity but also chi). radiosensitive, nonimmune phagocytosis appear to con­ tribute to the resistance against staphylococcal infec­ Procedures for Experimental Infection tion. Each mouse was inoculated subcutaneously with 0.1 ml of bacterial suspension into the back and the infected site was examined macro­ scopically 1, 2, 3, 5, 7, 10, 14, 21 and 27 days later.
    [Show full text]
  • The Transcription Factors Blimp-1 and IRF4 Jointly Control the Differentiation and Function of Effector Regulatory T Cells
    ARTICLES The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells Erika Cretney1,2,6, Annie Xin1,2,6, Wei Shi1,3, Martina Minnich4, Frederick Masson1,2, Maria Miasari1,2, Gabrielle T Belz1,2, Gordon K Smyth1,5, Meinrad Busslinger4, Stephen L Nutt1,2 & Axel Kallies1,2 Regulatory T cells (Treg cells) are required for peripheral tolerance. Evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with helper T cell differentiation. Here we demonstrate that expression of the transcription factor Blimp-1 defined a population of Treg cells that localized mainly to mucosal sites and produced IL-10. Blimp-1 was required for IL-10 production by these cells and for their tissue homeostasis. We provide evidence that the transcription factor IRF4, but not the transcription factor T-bet, was essential for Blimp-1 expression and for the differentiation of all effector Treg cells. Thus, our study defines a differentiation pathway that leads to the acquisition of Treg cell effector functions and requires both IRF4 and Blimp-1. + + Naturally occurring CD4 Foxp3 regulatory T cells (Treg cells) are Foxp3. The transcription factor IRF4 acts downstream of Foxp3, which derived from the thymus and are essential for the preservation of suggests that Treg cells use the transcriptional machinery of T helper 1,2 immune homeostasis and suppression of autoimmune pathology . type 2 (TH2) effector cells to specifically control this subset of helper 17 Treg cells depend on interleukin 2 (IL-2) for their maintenance and T cells .
    [Show full text]
  • 6510.Full.Pdf
    (CANCER RESEARCH 48. 6510-6516. November 15, 1988) Quantitative Studies on the Transplantability of Murine and Human Tumors into the Brain and Subcutaneous Tissues of NCr/Sed Nude Mice1 Anthony L. Zietman, Herman D. Suit,2 Jonathan R. Ramsay, Vlatko Silobrcic, and Robert S. Sedlacek Kdtt'in L. Steele Laboratory for Radiation Biology; Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 ABSTRACT (5, 6), and cyclophosphamide (7); with use of immunologically immature young animals (8-10); or with transplantation into The transplantability of experimental tumors into the brain (i.e.) and immunologically privileged sites such as the brain (11-13). s.c. tissues of C3Hf/Sed and athymic NCr/Sed nude mice was examined Nude mice, though athymic, do possess small numbers of T- using quantitative cell transplantation assays. Studies using the immune- competent Oil animals showed that brain is a more favorable site for cells (14, 15), which have been shown to be capable of cytotoxic the transplantation of syngeneic tumor than s.c. tissue and that this is allo- and xenoreactivity (16, 17). In addition, their numbers of true for nonimmunogenic as well as immunogenic tumors. The capacity splenic and nodal B-cells have been reported to be normal (9) of the brain to act as an immunological sanctuary can be overwhelmed or higher (15) than that found in hétérozygotes.Theactivity of by a strong, systemic, secondary immune response such as that evoked NK3 cells and peritoneal macrophages may also be higher (15, by the methylcholanthrene-induced sarcoma FSal. In studies performed 18, 19).
    [Show full text]
  • Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases
    International Journal of Molecular Sciences Review Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases Ali Youness 1,†, Charles-Henry Miquel 1,2,† and Jean-Charles Guéry 1,* 1 Infinity-Toulouse Institute for Infectious and Inflammatory Diseases, University of Toulouse, INSERM, CNRS, UPS, 31300 Toulouse, France; [email protected] (A.Y.); [email protected] (C.-H.M.) 2 Arthritis R&D, 92200 Neuilly-Sur-Seine, France * Correspondence: [email protected]; Tel.: +33-5-62-74-83-78; Fax: +33-5-62-74-45-58 † These authors contributed equally to this work. Abstract: Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells.
    [Show full text]
  • Sex Differences in Immune Responses
    REVIEWS Sex differences in immune responses Sabra L. Klein1 and Katie L. Flanagan2 Abstract | Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies. Sex is a biological variable that affects immune responses have 40% less viral RNA in their blood than men, men to both self and foreign antigens (for example, those show an almost twofold higher risk of death from from fungi, viruses, bacteria, parasites and allergens). malignant cancer than women and antibody responses The sex of an individual is defined by the differential to seasonal influenza vaccines are consistently at least organization of chromosomes, reproductive organs, twice as strong in women than men. Generally, adult and sex steroid levels; it is distinct from gender, which females mount stronger innate and adaptive immune includes behaviours and activities that are determined responses than males. This results in faster clearance of by society or culture in humans. Male and female differ­ pathogens and greater vaccine efficacy in females than ences in immunological responses may be influenced by in males but also contributes to their increased suscepti­ both sex and gender, with sex contributing to physio­logi­ bility to inflammatory and autoimmune diseases.
    [Show full text]
  • Role of Estrogen Receptor in Breast Cancer Cell Gene Expression
    4046 MOLECULAR MEDICINE REPORTS 13: 4046-4050, 2016 Role of estrogen receptor in breast cancer cell gene expression YABING ZHENG1, XIYING SHAO1, YUAN HUANG1, LEI SHI1, BO CHEN2, XIAOJIA WANG1, HONGJIAN YANG3, ZHANHONG CHEN1 and XIPING ZHANG3 Departments of 1Medical Oncology (Breast), 2Pathology and 3Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China Received April 28, 2015; Accepted February 23, 2016 DOI: 10.3892/mmr.2016.5018 Abstract. The aim of the present study was to establish the Europe in 2012, and the number of breast cancer-associated underlying regulatory mechanism of estrogen receptor (ER) mortalities is 131,000 (6). Furthermore, breast cancer is in breast cancer cell gene expression. A gene expression the most common cause of cancer-associated mortality in profile accession( no. GSE11324) was downloaded from the females. Therefore, it is essential to understand its molecular Gene Expression Omnibus (GEO) database. Differentially mechanism and develop more effective therapeutic methods expressed genes (DEGs) from an estrogen treatment group and for breast cancer treatment. a control group were identified. Chromatin immunoprecipita- The estrogen receptor (ER) is critical in determining the tion with high-throughput sequencing data (series GSE25710) phenotype of human breast cancers and is one of the most was obtained from the GEO for the ER binding sites, and important therapeutic targets (7). Furthermore, certain studies binding and expression target analysis was performed. A total have suggested that activation of ER is responsible for various of 3,122 DEGs were obtained and ER was demonstrated to biological processes, including cell growth and differentia- exhibit inhibition and activation roles during the regulation tion, and programmed cell death (8,9).
    [Show full text]
  • Promoter Through Interaction with the FOXP3 RORC2 Is Involved in T Cell Polarization
    RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter This information is current as Simone Burgler, Pierre-Yves Mantel, Claudio Bassin, Nadia of September 28, 2021. Ouaked, Cezmi A. Akdis and Carsten B. Schmidt-Weber J Immunol 2010; 184:6161-6169; Prepublished online 28 April 2010; doi: 10.4049/jimmunol.0903243 http://www.jimmunol.org/content/184/11/6161 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2010/04/28/jimmunol.090324 Material 3.DC1 http://www.jimmunol.org/ References This article cites 64 articles, 27 of which you can access for free at: http://www.jimmunol.org/content/184/11/6161.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 28, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *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 © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter Simone Burgler,* Pierre-Yves Mantel,*,† Claudio Bassin,* Nadia Ouaked,* Cezmi A.
    [Show full text]
  • Development, Maintenance and Functions of CD8+ T-Regulatory Cells
    Chakraborty S, Sa G. J Immunol Sci. (2018); 2(2): 8-12 Journal of Immunological Sciences Minireview Open Access Development, maintenance and functions of CD8+ T-regulatory cells: Molecular orchestration of FOXP3 transcription Sreeparna Chakraborty1 & Gaurisankar Sa1* 1Division of Molecular Medicine, Bose Institute, P-1/12, Calcutta Improvement Trust Scheme VII M, Kolkata 700054, India Article Info ABSTRACT Article Notes Modulation of immune cells to rejuvenate the immune responses Received: January 10, 2018 against cancer becomes a promising strategy for cancer therapy. T-regulatory Accepted: March 23, 2018 cells are one of the major hurdles in successful cancer immunotherapy. Recent + + *Correspondence: studies discovered that apart from CD4 Treg cells, CD8 Tregs also play roles in Prof. Gaurisankar Sa, Division of Molecular Medicine, Bose tumor immune evasion. Moreover, CD8+ Tregs shows synergistic immunosup- Institute, P-1/12, Calcutta Improvement Trust Scheme VII M, pression with CD4+ Treg cells in tumor microenvironment. Several phenotypic Kolkata 700 054, India; markers have been described for peripherally induced CD8+ Treg cells, but Tel: +91-33-2569-3258; till now no universal phenotypic signature has yet established. FOXP3 is the Fax: +91-33-2355-3886, E-mail: [email protected] master regulator of Treg cells and its transcription is critically regulated by pro- © 2018 Sa G. This article is distributed under the terms of the moter region as well as three intronic conserved non-coding regions, viz; CNS Creative Commons Attribution 4.0 International License. 1, 2 and 3. In this review, we have described the transcriptional networking associated with the regulation of FOXP3 in tumor-CD8+ Treg cells along with Keywords: CD4+ nTreg and iTreg cells.
    [Show full text]
  • Integrated Computational Approach to the Analysis of RNA-Seq Data Reveals New Transcriptional Regulators of Psoriasis
    OPEN Experimental & Molecular Medicine (2016) 48, e268; doi:10.1038/emm.2016.97 & 2016 KSBMB. All rights reserved 2092-6413/16 www.nature.com/emm ORIGINAL ARTICLE Integrated computational approach to the analysis of RNA-seq data reveals new transcriptional regulators of psoriasis Alena Zolotarenko1, Evgeny Chekalin1, Alexandre Mesentsev1, Ludmila Kiseleva2, Elena Gribanova2, Rohini Mehta3, Ancha Baranova3,4,5,6, Tatiana V Tatarinova6,7,8, Eleonora S Piruzian1 and Sergey Bruskin1,5 Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements. A comparative approach allowed us to identify 42 core transcriptional regulators of the disease associated with inflammation (NFκB, IRF9, JUN, FOS, SRF), the activity of T cells in psoriatic lesions (STAT6, FOXP3, NFATC2, GATA3, TCF7, RUNX1), the hyper- proliferation and migration of keratinocytes (JUN, FOS, NFIB, TFAP2A, TFAP2C) and lipid metabolism (TFAP2, RARA, VDR). In addition to the core regulators, we identified 38 transcription factors previously not associated with the disease that can clarify the pathogenesis of psoriasis. To illustrate these findings, we analyzed the regulatory role of one of the identified transcription factors (TFs), FOXA1. Using ChIP-seq and RNA-seq data, we concluded that the atypical expression of the FOXA1 TF is an important player in the disease as it inhibits the maturation of naive T cells into the (CD4+FOXA1+CD47+CD69+PD-L1(hi) FOXP3 − ) regulatory T cell subpopulation, therefore contributing to the development of psoriatic skin lesions.
    [Show full text]
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
    [Show full text]