Ezh2 Regulates Activation-Induced CD8+ T Cell Cycle Progression via Repressing Cdkn2a and Cdkn1c Expression.

Abstract:

:Transition from resting to cell cycle in response to antigenic stimulation is an essential step for naïve CD8+ T cells to differentiate to effector and memory cells. Leaving the resting state requires dramatic changes of chromatin status in the key cell cycle inhibitors but the details of these concerted events are not fully elucidated. Here, we showed that Ezh2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. Upon deletion of Ezh2 during thymocyte development (Ezh2fl/flCd4Cre+ mice), naive CD8+ T cells displayed impaired proliferation and increased apoptosis in response to antigen stimulation. However, naive CD8+ T cells only had impaired proliferation but no increase in apoptosis when Ezh2 was deleted after activation (Ezh2fl/flGzmBCre+ mice), suggesting cell cycle and apoptosis are temporally separable events controlled by Ezh2. We then showed that deletion of Ezh2 resulted in the increase in expression of cyclin-dependent kinase inhibitors Cdkn2a (p16 and Arf) and Cdkn1c (p57) in activated naïve CD8+ T cells as the consequence of reduced levels of H3K27me3 at these two gene loci. Finally, with real time imaging, we observed prolonged cell division times of naïve CD8+ T cells in the absence of Ezh2 post in vitro stimulation. Together, these findings reveal that repression of Cdkn1c and Cdkn2a by Ezh2 plays a critical role in execution of activation-induced CD8+ T cell proliferation.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Chen G,Subedi K,Chakraborty S,Sharov A,Lu J,Kim J,Mi X,Wersto R,Sung MH,Weng NP

doi

10.3389/fimmu.2018.00549

subject

Has Abstract

pub_date

2018-03-26 00:00:00

pages

549

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

    abstract::The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the inc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01821

    authors: Cho SF,Anderson KC,Tai YT

    更新日期:2018-08-10 00:00:00

  • ERdj5 in Innate Immune Cells Is a Crucial Factor for the Mucosal Adjuvanticity of Cholera Toxin.

    abstract::Cholera toxin (CT) is one of most strong mucosal adjuvants, but it cannot be clinically used owing to its toxicity. The cytosolic A1 subunit of CT (CTA1) is the molecule responsible for its immunostimulatory activity, which increases the concentration of cyclic AMP and causes the induction of pro-inflammatory cytokine...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01249

    authors: Kim MS,Yi EJ,Kim YI,Kim SH,Jung YS,Kim SR,Iwawaki T,Ko HJ,Chang SY

    更新日期:2019-06-04 00:00:00

  • Adipocyte Ceramides-The Nexus of Inflammation and Metabolic Disease.

    abstract::Adipose depots are heterogeneous tissues that store and sense fuel levels. Through the secretion of lipids, cytokines, and protein hormones (adipokines), they communicate with other organ systems, informing them of the organism's nutritional status. The adipose tissues include diverse types of adipocytes (white, beige...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.576347

    authors: Chaurasia B,Talbot CL,Summers SA

    更新日期:2020-09-23 00:00:00

  • Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions and Applications.

    abstract::In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.575712

    authors: Zhang B,Zhao M,Lu Q

    更新日期:2021-01-14 00:00:00

  • From Inflammasome to Exosome-Does Extracellular Vesicle Secretion Constitute an Inflammasome-Dependent Immune Response?

    abstract::Inflammasomes are intracellular protein complexes of pattern recognition receptors and caspase-1, with essential functions in regulating inflammatory responses of macrophages and dendritic cells. The primary role of inflammasomes is to catalyze processing and secretion of pro-inflammatory cytokines IL-1β and IL-18. Re...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02188

    authors: Cypryk W,Nyman TA,Matikainen S

    更新日期:2018-09-25 00:00:00

  • Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns.

    abstract::The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life's increased susceptibility to severe infections or until active immunity is achieved following infant's...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00338

    authors: Abu-Raya B,Smolen KK,Willems F,Kollmann TR,Marchant A

    更新日期:2016-08-31 00:00:00

  • Role of C5b-9 and RGC-32 in Cancer.

    abstract::The complement system represents an effective arsenal of innate immunity as well as an interface between innate and adaptive immunity. Activation of the complement system culminates with the assembly of the C5b-9 terminal complement complex on cell membranes, inducing target cell lysis. Translation of this sequence of...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01054

    authors: Vlaicu SI,Tatomir A,Rus V,Rus H

    更新日期:2019-05-09 00:00:00

  • Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment.

    abstract::Tumor-mediated regulation of the host immune system involves an intricate signaling network that results in the tumor's inherent survival benefit. Myeloid cells are central in orchestrating the mechanisms by which tumors escape immune detection and continue their proliferative programming. Myeloid cell activation has ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01842

    authors: Davidov V,Jensen G,Mai S,Chen SH,Pan PY

    更新日期:2020-09-02 00:00:00

  • Increased Expression on Innate Immune Factors in Placentas From HIV-Infected Mothers Concurs With Dampened Systemic Immune Activation.

    abstract::Innate immunity is one of the main protection mechanisms against viral infections, but how this system works at the maternal-fetal interface, especially during HIV infection, is still poorly known. In this study, we investigated the relationship between pregnancy and innate mechanisms associated with HIV immunity by e...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01822

    authors: Pereira NZ,Branco ACCC,Manfrere KCG,de Lima JF,Yoshikawa FSY,Milanez HMBPM,Pereira NV,Sotto MN,Duarte AJDS,Sato MN

    更新日期:2020-08-25 00:00:00

  • Comprehensive Characterization of a Next-Generation Antiviral T-Cell Product and Feasibility for Application in Immunosuppressed Transplant Patients.

    abstract::Viral infections have a major impact on morbidity and mortality of immunosuppressed solid organ transplant (SOT) patients because of missing or failure of adequate pharmacologic antiviral treatment. Adoptive antiviral T-cell therapy (AVTT), regenerating disturbed endogenous T-cell immunity, emerged as an attractive al...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01148

    authors: Amini L,Vollmer T,Wendering DJ,Jurisch A,Landwehr-Kenzel S,Otto NM,Jürchott K,Volk HD,Reinke P,Schmueck-Henneresse M

    更新日期:2019-05-28 00:00:00

  • Regulation of Intestinal Immune Responses through TLR Activation: Implications for Pro- and Prebiotics.

    abstract::The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs) are pattern recognition receptors exp...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00060

    authors: de Kivit S,Tobin MC,Forsyth CB,Keshavarzian A,Landay AL

    更新日期:2014-02-18 00:00:00

  • Mesothelioma in Familial Mediterranean Fever With Colchicine Intolerance: A Case Report and Literature Review.

    abstract::A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal im...

    journal_title:Frontiers in immunology

    pub_type:

    doi:10.3389/fimmu.2020.00889

    authors: Talerico R,Cardillo C,De Vito F,Schinzari F,Soldato M,Giustiniani MC,Verrecchia E,Manna R

    更新日期:2020-05-13 00:00:00

  • Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis.

    abstract::We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.02040

    authors: Zhang Q,Wang L,Jiang J,Lin S,Luo A,Zhao P,Tan W,Zhang M

    更新日期:2020-08-18 00:00:00

  • Zinc Oxide Nanowires Exposure Induces a Distinct Inflammatory Response via CCL11-Mediated Eosinophil Recruitment.

    abstract::High aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most important products in nanotechnology. The wide range applications of ZnONWs have heightened the need for evaluating the risks and biological consequences to these particles. In this study, we investigated inflammatory pathways activated by ZnO...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02604

    authors: Alghsham RS,Satpathy SR,Bodduluri SR,Hegde B,Jala VR,Twal W,Burlison JA,Sunkara M,Haribabu B

    更新日期:2019-11-08 00:00:00

  • Event-Driven Immunoprofiling Predicts Return of Disease Activity in Alemtuzumab-Treated Multiple Sclerosis.

    abstract::Background: Alemtuzumab is a highly effective drug for the treatment of multiple sclerosis (MS), characterized by specific patterns of depletion and repopulation. As an induction-like treatment concept, two mandatory infusion courses can inhibit long-term disease activity in the majority of patients, and additional co...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00056

    authors: Akgün K,Blankenburg J,Marggraf M,Haase R,Ziemssen T

    更新日期:2020-01-31 00:00:00

  • Respiratory Disease following Viral Lung Infection Alters the Murine Gut Microbiota.

    abstract::Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infectio...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00182

    authors: Groves HT,Cuthbertson L,James P,Moffatt MF,Cox MJ,Tregoning JS

    更新日期:2018-02-12 00:00:00

  • The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System.

    abstract::β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00673

    authors: Camilli G,Tabouret G,Quintin J

    更新日期:2018-04-16 00:00:00

  • Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries.

    abstract::Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01961

    authors: Corbett AJ,Awad W,Wang H,Chen Z

    更新日期:2020-08-27 00:00:00

  • Immune Cell-Type Specific Ablation of Adapter Protein ADAP Differentially Modulates EAE.

    abstract::The cytosolic adhesion and degranulation-promoting adapter protein ADAP is expressed in various hematopoietic cells including T cells, NK cells, myeloid cells, and platelets but absent in mature B cells. The role of ADAP in T cell activation, proliferation and integrin activation is well-accepted. We previously demons...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02343

    authors: Rudolph J,Meinke C,Voss M,Guttek K,Kliche S,Reinhold D,Schraven B,Reinhold A

    更新日期:2019-10-01 00:00:00

  • Additive or Synergistic Interactions Between IL-17A or IL-17F and TNF or IL-1β Depend on the Cell Type.

    abstract::Background: IL-17A has effects on several cell types and is a therapeutic target in several inflammatory diseases. IL-17F shares 50% homology and biological activities with IL-17A. It is now of interest to target both cytokines. The objective was to compare the IL-17A and IL-17F effect on cytokine production by RA syn...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01726

    authors: Noack M,Beringer A,Miossec P

    更新日期:2019-07-23 00:00:00

  • Protective and pathologic immune responses in human tegumentary leishmaniasis.

    abstract::Studies in the recent years have advanced the knowledge of how host and parasite factors contribute to the pathogenesis of human tegumentary leishmaniasis. Polymorphism within populations of Leishmania from the same species has been documented; indicating that infection with different strains may lead to distinct clin...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00301

    authors: Carvalho LP,Passos S,Schriefer A,Carvalho EM

    更新日期:2012-10-04 00:00:00

  • Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8(+) T-Regulatory Cells that Suppress SIV-Positive CD4(+) T-Cell Activation and Prevent SIV Infection in the Macaque Model.

    abstract::A new paradigm of mucosal vaccination against human immunodeficiency virus (HIV) infection has been investigated in the macaque model. A vaccine consisting of inactivated simian immunodeficiency virus (SIV)mac239 particles together with a living bacterial adjuvant (either the Calmette and Guerin bacillus, Lactobacillu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2014.00297

    authors: Andrieu JM,Chen S,Lai C,Guo W,Lu W

    更新日期:2014-06-30 00:00:00

  • Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies.

    abstract::Immunotherapies based on natural killer (NK) cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00745

    authors: Hofer E,Koehl U

    更新日期:2017-07-12 00:00:00

  • Diet-Induced Obesity Elicits Macrophage Infiltration and Reduction in Spine Density in the Hypothalami of Male but Not Female Mice.

    abstract::Increasing prevalence in obesity has become a significant public concern. C57BL/6J mice are prone to diet-induced obesity (DIO) when fed high-fat diet (HFD), and develop chronic inflammation and metabolic syndrome, making them a good model to analyze mechanisms whereby obesity elicits pathologies. DIO mice demonstrate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01992

    authors: Lainez NM,Jonak CR,Nair MG,Ethell IM,Wilson EH,Carson MJ,Coss D

    更新日期:2018-09-11 00:00:00

  • Immunoregulatory CD4(-)CD8(-) T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer.

    abstract::A central objective in organ transplantation and the treatment or prevention of autoimmune disease is the achievement of antigen-specific immune tolerance. An additional challenge in bone marrow transplantation for the treatment of hematological malignancies is the prevention of graft-vs-host disease (GVHD) while main...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2013.00006

    authors: Hillhouse EE,Delisle JS,Lesage S

    更新日期:2013-01-24 00:00:00

  • RNA Vaccines: A Suitable Platform for Tackling Emerging Pandemics?

    abstract::The COVID-19 pandemic demonstrates the ongoing threat of pandemics caused by novel, previously unrecognized, or mutated pathogens with high transmissibility. Currently, vaccine development is too slow for vaccines to be used in the control of emerging pandemics. RNA-based vaccines might be suitable to meet this challe...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.608460

    authors: Sandbrink JB,Shattock RJ

    更新日期:2020-12-22 00:00:00

  • CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter.

    abstract::CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, mul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00864

    authors: Kunkl M,Mastrogiovanni M,Porciello N,Caristi S,Monteleone E,Arcieri S,Tuosto L

    更新日期:2019-04-24 00:00:00

  • Mycobacterium bovis Bacillus Calmette-Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function.

    abstract::Intralesional Mycobacterium bovis bacillus Calmette-Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with in vitro studies to further...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00965

    authors: Lardone RD,Chan AA,Lee AF,Foshag LJ,Faries MB,Sieling PA,Lee DJ

    更新日期:2017-08-11 00:00:00

  • Alkaline pH Promotes NADPH Oxidase-Independent Neutrophil Extracellular Trap Formation: A Matter of Mitochondrial Reactive Oxygen Species Generation and Citrullination and Cleavage of Histone.

    abstract::pH is highly variable in different tissues and affects many enzymatic reactions in neutrophils. In response to calcium ionophores such as A23187 and ionomycin, neutrophils undergo nicotinamide adenine dinucleotide phosphate oxidase (NOX)-independent neutrophil extracellular trap (NET) formation (NETosis). However, how...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01849

    authors: Naffah de Souza C,Breda LCD,Khan MA,de Almeida SR,Câmara NOS,Sweezey N,Palaniyar N

    更新日期:2018-01-09 00:00:00

  • A Spectrum of Neural Autoantigens, Newly Identified by Histo-Immunoprecipitation, Mass Spectrometry, and Recombinant Cell-Based Indirect Immunofluorescence.

    abstract:Background:A plurality of neurological syndromes is associated with autoantibodies against neural antigens relevant for diagnosis and therapy. Identification of these antigens is crucial to understand the pathogenesis and to develop specific immunoassays. Using an indirect immunofluorescence assay (IFA)-based approach ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01447

    authors: Scharf M,Miske R,Kade S,Hahn S,Denno Y,Begemann N,Rochow N,Radzimski C,Brakopp S,Probst C,Teegen B,Stöcker W,Komorowski L

    更新日期:2018-07-09 00:00:00