Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-01-23

AUTHORS

Akinori Takaoka, Hideyuki Yanai, Seiji Kondo, Gordon Duncan, Hideo Negishi, Tatsuaki Mizutani, Shin-ichi Kano, Kenya Honda, Yusuke Ohba, Tak W. Mak, Tadatsugu Taniguchi

ABSTRACT

The activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity1,2,3. All TLRs use the adaptor MyD88 for signalling4, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully understood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR–MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-α. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-α induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR–MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses. More... »

PAGES

243-249

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature03308

DOI

http://dx.doi.org/10.1038/nature03308

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043058763

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15665823


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adaptor Proteins, Signal Transducing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antigens, Differentiation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cytokines", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Deletion", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Inflammation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Interferon Regulatory Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lipopolysaccharides", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Membrane Glycoproteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Myeloid Differentiation Factor 88", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Promoter Regions, Genetic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA, Messenger", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Cell Surface", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Immunologic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Shock, Septic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "TNF Receptor-Associated Factor 6", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Toll-Like Receptors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transcription Factors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Up-Regulation", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Takaoka", 
        "givenName": "Akinori", 
        "id": "sg:person.01137057770.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137057770.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yanai", 
        "givenName": "Hideyuki", 
        "id": "sg:person.01146230070.73", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01146230070.73"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada", 
          "id": "http://www.grid.ac/institutes/grid.231844.8", 
          "name": [
            "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kondo", 
        "givenName": "Seiji", 
        "id": "sg:person.01025525160.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01025525160.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada", 
          "id": "http://www.grid.ac/institutes/grid.231844.8", 
          "name": [
            "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Duncan", 
        "givenName": "Gordon", 
        "id": "sg:person.0632054517.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632054517.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Negishi", 
        "givenName": "Hideo", 
        "id": "sg:person.01260051143.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260051143.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mizutani", 
        "givenName": "Tatsuaki", 
        "id": "sg:person.0605165570.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605165570.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kano", 
        "givenName": "Shin-ichi", 
        "id": "sg:person.011703236477.12", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011703236477.12"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Honda", 
        "givenName": "Kenya", 
        "id": "sg:person.01315560470.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315560470.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Information and Cell Function, PRESTO, JST, 332-0012, KawaguchiSaitama, Japan", 
          "id": "http://www.grid.ac/institutes/grid.419082.6", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
            "Information and Cell Function, PRESTO, JST, 332-0012, KawaguchiSaitama, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ohba", 
        "givenName": "Yusuke", 
        "id": "sg:person.016622242425.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016622242425.02"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada", 
          "id": "http://www.grid.ac/institutes/grid.231844.8", 
          "name": [
            "Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mak", 
        "givenName": "Tak W.", 
        "id": "sg:person.014440054532.58", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014440054532.58"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan", 
          "id": "http://www.grid.ac/institutes/grid.26999.3d", 
          "name": [
            "Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Taniguchi", 
        "givenName": "Tadatsugu", 
        "id": "sg:person.0717046430.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717046430.02"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/35099560", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031094923", 
          "https://doi.org/10.1038/35099560"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35074106", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046017863", 
          "https://doi.org/10.1038/35074106"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature01850", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040742861", 
          "https://doi.org/10.1038/nature01850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1141", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041568711", 
          "https://doi.org/10.1038/ni1141"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nri1391", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023753307", 
          "https://doi.org/10.1038/nri1391"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35100529", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008398067", 
          "https://doi.org/10.1038/35100529"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02738", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052167491", 
          "https://doi.org/10.1038/nature02738"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/383443a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047504524", 
          "https://doi.org/10.1038/383443a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni1118", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015476375", 
          "https://doi.org/10.1038/ni1118"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2005-01-23", 
    "datePublishedReg": "2005-01-23", 
    "description": "The activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity1,2,3. All TLRs use the adaptor MyD88 for signalling4, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully understood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR\u2013MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-\u03b1. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-\u03b1 induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR\u2013MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/nature03308", 
    "inLanguage": "en", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0028-0836", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7030", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "434"
      }
    ], 
    "keywords": [
      "Toll-like receptors", 
      "TLR-MyD88", 
      "gene induction program", 
      "proinflammatory cytokines", 
      "tumor-necrosis factor", 
      "harmful immune responses", 
      "serum levels", 
      "TLR ligands", 
      "TLR activation", 
      "lethal shock", 
      "cytokine gene transcription", 
      "immune response", 
      "adaptor MyD88", 
      "therapeutic intervention", 
      "IRF5 gene", 
      "cytokines", 
      "IRF-5", 
      "potential target", 
      "nuclear translocation", 
      "interleukin-6", 
      "MyD88", 
      "haematopoietic cells", 
      "receptors", 
      "induction", 
      "integral role", 
      "downstream regulators", 
      "activation", 
      "IL-12", 
      "gene induction", 
      "interferon", 
      "show resistance", 
      "gene transcription", 
      "mice", 
      "pathway", 
      "lipopolysaccharide", 
      "TRAF6", 
      "intervention", 
      "induction programs", 
      "cells", 
      "response", 
      "program", 
      "evidence", 
      "decrease", 
      "factors", 
      "levels", 
      "translocation", 
      "target", 
      "shock", 
      "role", 
      "genes", 
      "resistance", 
      "regulator", 
      "mechanism", 
      "transcription", 
      "DNA", 
      "ligands", 
      "downstream", 
      "signalling4", 
      "MyD88-mediated gene induction programme", 
      "transcription factor IRF-5", 
      "factor IRF-5", 
      "Irf5-/- mice show resistance", 
      "study identifies IRF-5", 
      "identifies IRF-5", 
      "principal downstream regulator"
    ], 
    "name": "Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors", 
    "pagination": "243-249", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1043058763"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature03308"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "15665823"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature03308", 
      "https://app.dimensions.ai/details/publication/pub.1043058763"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2021-11-01T18:08", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20211101/entities/gbq_results/article/article_410.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/nature03308"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature03308'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature03308'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature03308'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature03308'


 

This table displays all metadata directly associated to this object as RDF triples.

324 TRIPLES      22 PREDICATES      121 URIs      104 LITERALS      28 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature03308 schema:about N0473b1af59684db695184656cbc0912d
2 N1cc243b2c7e24a9eaed97dff16cb41b8
3 N237be44cc2134f198e8efbe0e81e7aba
4 N23911aa69578485a9c87b56fc2b7cd67
5 N3a9cefa056c74cfba2d700481eb08d09
6 N52e0cf5cfe5748ed8dba110fea18fb34
7 N58be582bd8754eeb9978d91fdcebeeef
8 N5d837fdb17254f8bbc0e1d7e5e2d4898
9 N73db52cfa26f4ef3aa0d2f3d719e7516
10 N97f344e9b4f146d081e874af13a3d53d
11 Na05191bb6e6d4f998c905b0dd6f82c6d
12 Na2a5c74b3de343cba9f4f8299b1f133b
13 Na9b3b31222c44dafba4adc9632f8bd5f
14 Nae5ff8e142e043c3a020e597abf2e611
15 Naf2e9249d4a04c0bbcdaabbd2ae6db5c
16 Nb3bb31685a7d48baa1e416609fbf4ed3
17 Nc58d5cbe13094c3680ceedde0e3225e0
18 Ncdef4f39ef6b4ec2b5e9e8ff15410c9a
19 Nee82afdf9f14416f86bea8f3ede3d26a
20 Nfcd2464135b14846abc7071605c6de58
21 Nfcdb6f31f7734bc9a09b1444ff5d0f6c
22 anzsrc-for:11
23 anzsrc-for:1107
24 schema:author N5a1a9aba838d4e178261eaefa6b29632
25 schema:citation sg:pub.10.1038/35074106
26 sg:pub.10.1038/35099560
27 sg:pub.10.1038/35100529
28 sg:pub.10.1038/383443a0
29 sg:pub.10.1038/nature01850
30 sg:pub.10.1038/nature02738
31 sg:pub.10.1038/ni1118
32 sg:pub.10.1038/ni1141
33 sg:pub.10.1038/nri1391
34 schema:datePublished 2005-01-23
35 schema:datePublishedReg 2005-01-23
36 schema:description The activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity1,2,3. All TLRs use the adaptor MyD88 for signalling4, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully understood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR–MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-α. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-α induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR–MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.
37 schema:genre article
38 schema:inLanguage en
39 schema:isAccessibleForFree false
40 schema:isPartOf N005806b6d7ed4af999412cb9f1cac2a8
41 N9a619530ab5e42fd8d210e7e5036b9cd
42 sg:journal.1018957
43 schema:keywords DNA
44 IL-12
45 IRF-5
46 IRF5 gene
47 Irf5-/- mice show resistance
48 MyD88
49 MyD88-mediated gene induction programme
50 TLR activation
51 TLR ligands
52 TLR-MyD88
53 TRAF6
54 Toll-like receptors
55 activation
56 adaptor MyD88
57 cells
58 cytokine gene transcription
59 cytokines
60 decrease
61 downstream
62 downstream regulators
63 evidence
64 factor IRF-5
65 factors
66 gene induction
67 gene induction program
68 gene transcription
69 genes
70 haematopoietic cells
71 harmful immune responses
72 identifies IRF-5
73 immune response
74 induction
75 induction programs
76 integral role
77 interferon
78 interleukin-6
79 intervention
80 lethal shock
81 levels
82 ligands
83 lipopolysaccharide
84 mechanism
85 mice
86 nuclear translocation
87 pathway
88 potential target
89 principal downstream regulator
90 program
91 proinflammatory cytokines
92 receptors
93 regulator
94 resistance
95 response
96 role
97 serum levels
98 shock
99 show resistance
100 signalling4
101 study identifies IRF-5
102 target
103 therapeutic intervention
104 transcription
105 transcription factor IRF-5
106 translocation
107 tumor-necrosis factor
108 schema:name Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors
109 schema:pagination 243-249
110 schema:productId N26958b3c804e4ed3b6d875b0855737f4
111 Nc5ccd3951e154050962fc845e6e0ab4e
112 Nf310b438d94a4a6dbb481058734c2601
113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043058763
114 https://doi.org/10.1038/nature03308
115 schema:sdDatePublished 2021-11-01T18:08
116 schema:sdLicense https://scigraph.springernature.com/explorer/license/
117 schema:sdPublisher N34b0d690a94449fc929c1460bed6a4ce
118 schema:url https://doi.org/10.1038/nature03308
119 sgo:license sg:explorer/license/
120 sgo:sdDataset articles
121 rdf:type schema:ScholarlyArticle
122 N005806b6d7ed4af999412cb9f1cac2a8 schema:issueNumber 7030
123 rdf:type schema:PublicationIssue
124 N0473b1af59684db695184656cbc0912d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
125 schema:name Interferon Regulatory Factors
126 rdf:type schema:DefinedTerm
127 N0b8e4ebd75a340409a2b3e509911fc6c rdf:first sg:person.01315560470.25
128 rdf:rest N19afb28d7a014efcbf71dffadc0078fe
129 N19afb28d7a014efcbf71dffadc0078fe rdf:first sg:person.016622242425.02
130 rdf:rest Nc3c2235eebaf44bb9cb80da217240799
131 N1cc243b2c7e24a9eaed97dff16cb41b8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Receptors, Cell Surface
133 rdf:type schema:DefinedTerm
134 N237be44cc2134f198e8efbe0e81e7aba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Animals
136 rdf:type schema:DefinedTerm
137 N23911aa69578485a9c87b56fc2b7cd67 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Adaptor Proteins, Signal Transducing
139 rdf:type schema:DefinedTerm
140 N26958b3c804e4ed3b6d875b0855737f4 schema:name dimensions_id
141 schema:value pub.1043058763
142 rdf:type schema:PropertyValue
143 N34b0d690a94449fc929c1460bed6a4ce schema:name Springer Nature - SN SciGraph project
144 rdf:type schema:Organization
145 N3a9cefa056c74cfba2d700481eb08d09 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Membrane Glycoproteins
147 rdf:type schema:DefinedTerm
148 N40bc80c7c4034569bd446783148aa379 rdf:first sg:person.01146230070.73
149 rdf:rest N71a66206b88b45eab6e163b17fd21fcb
150 N4b2393e7864f4377ae60819bfe3f214d rdf:first sg:person.0605165570.90
151 rdf:rest Naafd7280f8404bc09a7eefa3b285e94d
152 N52e0cf5cfe5748ed8dba110fea18fb34 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Toll-Like Receptors
154 rdf:type schema:DefinedTerm
155 N58be582bd8754eeb9978d91fdcebeeef schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Signal Transduction
157 rdf:type schema:DefinedTerm
158 N5a1a9aba838d4e178261eaefa6b29632 rdf:first sg:person.01137057770.02
159 rdf:rest N40bc80c7c4034569bd446783148aa379
160 N5d837fdb17254f8bbc0e1d7e5e2d4898 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Up-Regulation
162 rdf:type schema:DefinedTerm
163 N71a66206b88b45eab6e163b17fd21fcb rdf:first sg:person.01025525160.71
164 rdf:rest N7330bbd634a644c68173f9215dd0b2db
165 N7330bbd634a644c68173f9215dd0b2db rdf:first sg:person.0632054517.44
166 rdf:rest N7828336abecf46a68d2c15bc4e46da8c
167 N73db52cfa26f4ef3aa0d2f3d719e7516 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
168 schema:name Myeloid Differentiation Factor 88
169 rdf:type schema:DefinedTerm
170 N7828336abecf46a68d2c15bc4e46da8c rdf:first sg:person.01260051143.89
171 rdf:rest N4b2393e7864f4377ae60819bfe3f214d
172 N97f344e9b4f146d081e874af13a3d53d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Cytokines
174 rdf:type schema:DefinedTerm
175 N9a619530ab5e42fd8d210e7e5036b9cd schema:volumeNumber 434
176 rdf:type schema:PublicationVolume
177 Na05191bb6e6d4f998c905b0dd6f82c6d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Shock, Septic
179 rdf:type schema:DefinedTerm
180 Na2a5c74b3de343cba9f4f8299b1f133b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
181 schema:name Inflammation
182 rdf:type schema:DefinedTerm
183 Na9b3b31222c44dafba4adc9632f8bd5f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Antigens, Differentiation
185 rdf:type schema:DefinedTerm
186 Naafd7280f8404bc09a7eefa3b285e94d rdf:first sg:person.011703236477.12
187 rdf:rest N0b8e4ebd75a340409a2b3e509911fc6c
188 Nae5ff8e142e043c3a020e597abf2e611 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Mice
190 rdf:type schema:DefinedTerm
191 Naf2e9249d4a04c0bbcdaabbd2ae6db5c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name Receptors, Immunologic
193 rdf:type schema:DefinedTerm
194 Nb3bb31685a7d48baa1e416609fbf4ed3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
195 schema:name RNA, Messenger
196 rdf:type schema:DefinedTerm
197 Nc3c2235eebaf44bb9cb80da217240799 rdf:first sg:person.014440054532.58
198 rdf:rest Ne79eb358d65f4ba9bb498b20e33f016b
199 Nc58d5cbe13094c3680ceedde0e3225e0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
200 schema:name TNF Receptor-Associated Factor 6
201 rdf:type schema:DefinedTerm
202 Nc5ccd3951e154050962fc845e6e0ab4e schema:name pubmed_id
203 schema:value 15665823
204 rdf:type schema:PropertyValue
205 Ncdef4f39ef6b4ec2b5e9e8ff15410c9a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
206 schema:name Lipopolysaccharides
207 rdf:type schema:DefinedTerm
208 Ne79eb358d65f4ba9bb498b20e33f016b rdf:first sg:person.0717046430.02
209 rdf:rest rdf:nil
210 Nee82afdf9f14416f86bea8f3ede3d26a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
211 schema:name Gene Deletion
212 rdf:type schema:DefinedTerm
213 Nf310b438d94a4a6dbb481058734c2601 schema:name doi
214 schema:value 10.1038/nature03308
215 rdf:type schema:PropertyValue
216 Nfcd2464135b14846abc7071605c6de58 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
217 schema:name Transcription Factors
218 rdf:type schema:DefinedTerm
219 Nfcdb6f31f7734bc9a09b1444ff5d0f6c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
220 schema:name Promoter Regions, Genetic
221 rdf:type schema:DefinedTerm
222 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
223 schema:name Medical and Health Sciences
224 rdf:type schema:DefinedTerm
225 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
226 schema:name Immunology
227 rdf:type schema:DefinedTerm
228 sg:journal.1018957 schema:issn 0028-0836
229 1476-4687
230 schema:name Nature
231 schema:publisher Springer Nature
232 rdf:type schema:Periodical
233 sg:person.01025525160.71 schema:affiliation grid-institutes:grid.231844.8
234 schema:familyName Kondo
235 schema:givenName Seiji
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01025525160.71
237 rdf:type schema:Person
238 sg:person.01137057770.02 schema:affiliation grid-institutes:grid.26999.3d
239 schema:familyName Takaoka
240 schema:givenName Akinori
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137057770.02
242 rdf:type schema:Person
243 sg:person.01146230070.73 schema:affiliation grid-institutes:grid.26999.3d
244 schema:familyName Yanai
245 schema:givenName Hideyuki
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01146230070.73
247 rdf:type schema:Person
248 sg:person.011703236477.12 schema:affiliation grid-institutes:grid.26999.3d
249 schema:familyName Kano
250 schema:givenName Shin-ichi
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011703236477.12
252 rdf:type schema:Person
253 sg:person.01260051143.89 schema:affiliation grid-institutes:grid.26999.3d
254 schema:familyName Negishi
255 schema:givenName Hideo
256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01260051143.89
257 rdf:type schema:Person
258 sg:person.01315560470.25 schema:affiliation grid-institutes:grid.26999.3d
259 schema:familyName Honda
260 schema:givenName Kenya
261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315560470.25
262 rdf:type schema:Person
263 sg:person.014440054532.58 schema:affiliation grid-institutes:grid.231844.8
264 schema:familyName Mak
265 schema:givenName Tak W.
266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014440054532.58
267 rdf:type schema:Person
268 sg:person.016622242425.02 schema:affiliation grid-institutes:grid.419082.6
269 schema:familyName Ohba
270 schema:givenName Yusuke
271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016622242425.02
272 rdf:type schema:Person
273 sg:person.0605165570.90 schema:affiliation grid-institutes:grid.26999.3d
274 schema:familyName Mizutani
275 schema:givenName Tatsuaki
276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0605165570.90
277 rdf:type schema:Person
278 sg:person.0632054517.44 schema:affiliation grid-institutes:grid.231844.8
279 schema:familyName Duncan
280 schema:givenName Gordon
281 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0632054517.44
282 rdf:type schema:Person
283 sg:person.0717046430.02 schema:affiliation grid-institutes:grid.26999.3d
284 schema:familyName Taniguchi
285 schema:givenName Tadatsugu
286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0717046430.02
287 rdf:type schema:Person
288 sg:pub.10.1038/35074106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046017863
289 https://doi.org/10.1038/35074106
290 rdf:type schema:CreativeWork
291 sg:pub.10.1038/35099560 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031094923
292 https://doi.org/10.1038/35099560
293 rdf:type schema:CreativeWork
294 sg:pub.10.1038/35100529 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008398067
295 https://doi.org/10.1038/35100529
296 rdf:type schema:CreativeWork
297 sg:pub.10.1038/383443a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047504524
298 https://doi.org/10.1038/383443a0
299 rdf:type schema:CreativeWork
300 sg:pub.10.1038/nature01850 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040742861
301 https://doi.org/10.1038/nature01850
302 rdf:type schema:CreativeWork
303 sg:pub.10.1038/nature02738 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052167491
304 https://doi.org/10.1038/nature02738
305 rdf:type schema:CreativeWork
306 sg:pub.10.1038/ni1118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015476375
307 https://doi.org/10.1038/ni1118
308 rdf:type schema:CreativeWork
309 sg:pub.10.1038/ni1141 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041568711
310 https://doi.org/10.1038/ni1141
311 rdf:type schema:CreativeWork
312 sg:pub.10.1038/nri1391 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023753307
313 https://doi.org/10.1038/nri1391
314 rdf:type schema:CreativeWork
315 grid-institutes:grid.231844.8 schema:alternateName Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada
316 schema:name Campbell Family Institute of Breast Cancer Research, University of Toronto, 610 University Avenue, Room 7-411, M5G 2M9, Ontario, Toronto, Canada
317 rdf:type schema:Organization
318 grid-institutes:grid.26999.3d schema:alternateName Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan
319 schema:name Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan
320 rdf:type schema:Organization
321 grid-institutes:grid.419082.6 schema:alternateName Information and Cell Function, PRESTO, JST, 332-0012, KawaguchiSaitama, Japan
322 schema:name Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan
323 Information and Cell Function, PRESTO, JST, 332-0012, KawaguchiSaitama, Japan
324 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...