Two isoforms of otubain 1 regulate T cell anergy via GRAIL.

Abstract:

:The active ubiquitin E3 ligase GRAIL is crucial in the induction of CD4 T cell anergy. Here we show that GRAIL is associated with and regulated by two isoforms of the ubiquitin-specific protease otubain 1. In lethally irradiated mice reconstituted with bone marrow cells from T cell receptor-transgenic mice retrovirally transduced to express the genes encoding these proteases, otubain 1-expressing cells contained negligible amounts of endogenous GRAIL, proliferated well and produced large amounts of interleukin 2 after antigenic stimulation. In contrast, cells expressing the alternatively spliced isoform, otubain 1 alternative reading frame 1, contained large amounts of endogenous GRAIL and were functionally anergic, and they proliferated poorly and produced undetectable interleukin 2 when stimulated in a similar way. Thus, these two proteins have opposing epistatic functions in controlling the stability of GRAIL expression and the resultant anergy phenotype in T cells.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Soares L,Seroogy C,Skrenta H,Anandasabapathy N,Lovelace P,Chung CD,Engleman E,Fathman CG

doi

10.1038/ni1017

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

45-54

issue

1

eissn

1529-2908

issn

1529-2916

pii

ni1017

journal_volume

5

pub_type

杂志文章
  • Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion.

    abstract::The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a res...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0793-3

    authors: Yu YR,Imrichova H,Wang H,Chao T,Xiao Z,Gao M,Rincon-Restrepo M,Franco F,Genolet R,Cheng WC,Jandus C,Coukos G,Jiang YF,Locasale JW,Zippelius A,Liu PS,Tang L,Bock C,Vannini N,Ho PC

    更新日期:2020-12-01 00:00:00

  • Genetic variation in Toll-like receptors and disease susceptibility.

    abstract::Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2284

    authors: Netea MG,Wijmenga C,O'Neill LA

    更新日期:2012-05-18 00:00:00

  • F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation.

    abstract::The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2341

    authors: Zhao J,Wei J,Mialki RK,Mallampalli DF,Chen BB,Coon T,Zou C,Mallampalli RK,Zhao Y

    更新日期:2012-06-03 00:00:00

  • Duration of TCR signaling controls CD4-CD8 lineage differentiation in vivo.

    abstract::The duration of T cell receptor (TCR) signaling is thought to be important for thymocyte differentiation into the CD4 or CD8 lineage. However, the in vivo relevance of this hypothesis is unclear. Here we divided T cell positive selection into genetically separable developmental steps by confining TCR signal transducti...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1040

    authors: Liu X,Bosselut R

    更新日期:2004-03-01 00:00:00

  • The nuclear receptor LXRα controls the functional specialization of splenic macrophages.

    abstract::Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2622

    authors: A-Gonzalez N,Guillen JA,Gallardo G,Diaz M,de la Rosa JV,Hernandez IH,Casanova-Acebes M,Lopez F,Tabraue C,Beceiro S,Hong C,Lara PC,Andujar M,Arai S,Miyazaki T,Li S,Corbi AL,Tontonoz P,Hidalgo A,Castrillo A

    更新日期:2013-08-01 00:00:00

  • A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production.

    abstract::MicroRNAs (miRNAs) exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. We sought to identify miRNAs and miRNA-regulated pathways that control the type 2 helper T cell (TH2 cell) responses that drive pathogenic inflammation in asthma. Profiling miRNA expre...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3026

    authors: Simpson LJ,Patel S,Bhakta NR,Choy DF,Brightbill HD,Ren X,Wang Y,Pua HH,Baumjohann D,Montoya MM,Panduro M,Remedios KA,Huang X,Fahy JV,Arron JR,Woodruff PG,Ansel KM

    更新日期:2014-12-01 00:00:00

  • Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice.

    abstract::Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than th...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni801

    authors: Ujike A,Takeda K,Nakamura A,Ebihara S,Akiyama K,Takai T

    更新日期:2002-06-01 00:00:00

  • A tissue checkpoint regulates type 2 immunity.

    abstract::Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were m...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3582

    authors: Van Dyken SJ,Nussbaum JC,Lee J,Molofsky AB,Liang HE,Pollack JL,Gate RE,Haliburton GE,Ye CJ,Marson A,Erle DJ,Locksley RM

    更新日期:2016-12-01 00:00:00

  • Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins.

    abstract::Nonmuscle myosin light-chain kinase (MYLK) mediates increased lung vascular endothelial permeability in lipopolysaccharide-induced lung inflammatory injury, the chief cause of the acute respiratory distress syndrome. In a lung injury model, we demonstrate here that MYLK was also essential for neutrophil transmigration...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1628

    authors: Xu J,Gao XP,Ramchandran R,Zhao YY,Vogel SM,Malik AB

    更新日期:2008-08-01 00:00:00

  • An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.

    abstract::The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream'...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1635

    authors: Yu MC,Su LL,Zou L,Liu Y,Wu N,Kong L,Zhuang ZH,Sun L,Liu HP,Hu JH,Li D,Strominger JL,Zang JW,Pei G,Ge BX

    更新日期:2008-08-01 00:00:00

  • Transcriptional insights into the CD8(+) T cell response to infection and memory T cell formation.

    abstract::After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putati...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2536

    authors: Best JA,Blair DA,Knell J,Yang E,Mayya V,Doedens A,Dustin ML,Goldrath AW,Immunological Genome Project Consortium.

    更新日期:2013-04-01 00:00:00

  • The transcription factor musculin promotes the unidirectional development of peripheral Treg cells by suppressing the TH2 transcriptional program.

    abstract::Although master transcription factors (TFs) are key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress the development of other, non-specific T cell lineages has not been fully elucidated. Through the use of regulatory T ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3667

    authors: Wu C,Chen Z,Dardalhon V,Xiao S,Thalhamer T,Liao M,Madi A,Franca RF,Han T,Oukka M,Kuchroo V

    更新日期:2017-03-01 00:00:00

  • PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils.

    abstract::Neutrophils encounter and 'prioritize' many chemoattractants in their pursuit of bacteria. Here we tested the possibility that the phosphatase PTEN is responsible for the prioritization of chemoattractants. Neutrophils induced chemotaxis by two separate pathways, the phosphatidylinositol-3-OH kinase (PI(3)K) phosphata...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1623

    authors: Heit B,Robbins SM,Downey CM,Guan Z,Colarusso P,Miller BJ,Jirik FR,Kubes P

    更新日期:2008-07-01 00:00:00

  • Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation.

    abstract::Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (T(FH) cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the T(H)17 subset of helper T cells in the lungs...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3008

    authors: Jeltsch KM,Hu D,Brenner S,Zöller J,Heinz GA,Nagel D,Vogel KU,Rehage N,Warth SC,Edelmann SL,Gloury R,Martin N,Lohs C,Lech M,Stehklein JE,Geerlof A,Kremmer E,Weber A,Anders HJ,Schmitz I,Schmidt-Supprian M,Fu M,H

    更新日期:2014-11-01 00:00:00

  • T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2.

    abstract::The lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1506

    authors: Tanaka Y,Hamano S,Gotoh K,Murata Y,Kunisaki Y,Nishikimi A,Takii R,Kawaguchi M,Inayoshi A,Masuko S,Himeno K,Sasazuki T,Fukui Y

    更新日期:2007-10-01 00:00:00

  • Author Correction: Tissue patrol by resident memory CD8+ T cells in human skin.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41590-020-0665-x

    authors: Dijkgraaf FE,Matos TR,Hoogenboezem M,Toebes M,Vredevoogd DW,Mertz M,van den Broek B,Song JY,Teunissen MBM,Luiten RM,Beltman JB,Schumacher TN

    更新日期:2020-06-01 00:00:00

  • The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.

    abstract::The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells show...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2834

    authors: Kurachi M,Barnitz RA,Yosef N,Odorizzi PM,DiIorio MA,Lemieux ME,Yates K,Godec J,Klatt MG,Regev A,Wherry EJ,Haining WN

    更新日期:2014-04-01 00:00:00

  • Costimulatory blockade by the induction of an endogenous xenospecific antibody response.

    abstract::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/77853

    authors: Rogers NJ,Mirenda V,Jackson I,Dorling A,Lechler RI

    更新日期:2000-08-01 00:00:00

  • Regulation of naive T cell function by the NF-kappaB2 pathway.

    abstract::T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects....

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1351

    authors: Ishimaru N,Kishimoto H,Hayashi Y,Sprent J

    更新日期:2006-07-01 00:00:00

  • Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells.

    abstract::The cellular dynamics of the egress of lymphocytes from lymph nodes are poorly defined. Here we visualized the branched organization of lymph node cortical sinuses and found that after entry, some T cells were retained, whereas others returned to the parenchyma. T cells deficient in sphingosine 1-phosphate receptor ty...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1682

    authors: Grigorova IL,Schwab SR,Phan TG,Pham TH,Okada T,Cyster JG

    更新日期:2009-01-01 00:00:00

  • Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.

    abstract::DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1204

    authors: Hamerman JA,Tchao NK,Lowell CA,Lanier LL

    更新日期:2005-06-01 00:00:00

  • The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues.

    abstract::Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni860

    authors: York IA,Chang SC,Saric T,Keys JA,Favreau JM,Goldberg AL,Rock KL

    更新日期:2002-12-01 00:00:00

  • CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation.

    abstract::CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell act...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni830

    authors: Gaide O,Favier B,Legler DF,Bonnet D,Brissoni B,Valitutti S,Bron C,Tschopp J,Thome M

    更新日期:2002-09-01 00:00:00

  • CSF-1R, DAP12 and beta-catenin: a ménage à trois.

    abstract::DAP12-coupled receptors influence signals emanating from Toll-like receptors, integrins and receptors for cytokines and growth factors. New findings indicate that DAP12 also facilitates the ability of CSF-1R, the receptor for M-CSF, to induce the stabilization and nuclear translocation of beta-catenin. ...

    journal_title:Nature immunology

    pub_type: 新闻

    doi:10.1038/ni0709-681

    authors: McVicar DW,Trinchieri G

    更新日期:2009-07-01 00:00:00

  • Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.

    abstract::Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalizat...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1168

    authors: Gomez TS,Hamann MJ,McCarney S,Savoy DN,Lubking CM,Heldebrant MP,Labno CM,McKean DJ,McNiven MA,Burkhardt JK,Billadeau DD

    更新日期:2005-03-01 00:00:00

  • The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells.

    abstract::Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous admi...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2352

    authors: Kanaya T,Hase K,Takahashi D,Fukuda S,Hoshino K,Sasaki I,Hemmi H,Knoop KA,Kumar N,Sato M,Katsuno T,Yokosuka O,Toyooka K,Nakai K,Sakamoto A,Kitahara Y,Jinnohara T,McSorley SJ,Kaisho T,Williams IR,Ohno H

    更新日期:2012-06-17 00:00:00

  • Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

    abstract::Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to a...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0347-8

    authors: Altman MC,Gill MA,Whalen E,Babineau DC,Shao B,Liu AH,Jepson B,Gruchalla RS,O'Connor GT,Pongracic JA,Kercsmar CM,Khurana Hershey GK,Zoratti EM,Johnson CC,Teach SJ,Kattan M,Bacharier LB,Beigelman A,Sigelman SM,Presnel

    更新日期:2019-05-01 00:00:00

  • Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges.

    abstract::Vaccines can have nonspecific effects through their modulation of responses to infections not specifically targeted by the vaccine. However, lack of knowledge about the underlying immunological mechanisms and molecular cause-and-effect relationships prevent use of this potentially powerful early-life intervention to i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2961

    authors: Aaby P,Kollmann TR,Benn CS

    更新日期:2014-10-01 00:00:00

  • Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI.

    abstract::Chemoattractant-stimulated granule release from neutrophils, basophils and eosinophils is critical for the innate immune response against infectious bacteria. Interleukin 8 (IL-8) activation of the chemokine receptor CXCRI was found to stimulate rapid formation of beta-arrestin complexes with Hck or c-Fgr. Formation o...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/79767

    authors: Barlic J,Andrews JD,Kelvin AA,Bosinger SE,DeVries ME,Xu L,Dobransky T,Feldman RD,Ferguson SS,Kelvin DJ

    更新日期:2000-09-01 00:00:00

  • Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development.

    abstract::B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in hum...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0772-8

    authors: Burrows N,Bashford-Rogers RJM,Bhute VJ,Peñalver A,Ferdinand JR,Stewart BJ,Smith JEG,Deobagkar-Lele M,Giudice G,Connor TM,Inaba A,Bergamaschi L,Smith S,Tran MGB,Petsalaki E,Lyons PA,Espeli M,Huntly BJP,Smith KGC,Corn

    更新日期:2020-11-01 00:00:00