The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2019
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Molecular Immunology. 2019, 108, pp. 111-120. ISSN 0161-5890. eISSN 1872-9142. Available under: doi: 10.1016/j.molimm.2019.02.010
Zusammenfassung

FAT10 is the only ubiquitin-like modifier which directly targets its substrate proteins for rapid degradation by the proteasome. While the conjugation and proteasomal targeting of FAT10 are fairly well understood, the biological functions of FAT10 have remained largely elusive. Here we have investigated the role of FAT10 in cytokine responses in mice upon viral infection. We used lymphocytic choriomeningitis virus (LCMV) infection of mice to induce the IFN-γ and TNF-α-dependent expression of FAT10. We found that TCR-stimulated splenocytes derived from LCMV-infected FAT10-/- mice secreted less IFN-γ and expressed less mRNA for IL-12 p40 but secreted more IFN-α and IFN-β compared to FAT10+/- mice. The reduction in IFN-γ secretion could be assigned to CD8+ T cells. Nevertheless, LCMV viral clearance was similar in FAT10-/- as compared to FAT10+/- mice. Since FAT10 has previously been reported to promote influenza A virus (IAV) replication in vitro we have studied the effect of FAT10 deficiency during IAV infection in mice. Unexpectedly, IAV titers and disease symptoms were not changed in FAT10-/- mice even though the Fat10 mRNA was rapidly induced in the lung upon IAV infection. In conclusion, we find that FAT10 fine-tunes the balance of interferons during viral infection by lowering the production of type I and enhancing type II interferons.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
FAT10, Ubiquitin-like modifier, LCMV, IAV, Interferon response
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690MAH, Mei Min, Michael BASLER, Marcus GRÖTTRUP, 2019. The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8+ T cells. In: Molecular Immunology. 2019, 108, pp. 111-120. ISSN 0161-5890. eISSN 1872-9142. Available under: doi: 10.1016/j.molimm.2019.02.010
BibTex
@article{Mah2019-04ubiqu-45521,
  year={2019},
  doi={10.1016/j.molimm.2019.02.010},
  title={The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8<sup>+</sup> T cells},
  volume={108},
  issn={0161-5890},
  journal={Molecular Immunology},
  pages={111--120},
  author={Mah, Mei Min and Basler, Michael and Gröttrup, Marcus}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/45521">
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/45521"/>
    <dc:contributor>Mah, Mei Min</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:abstract xml:lang="eng">FAT10 is the only ubiquitin-like modifier which directly targets its substrate proteins for rapid degradation by the proteasome. While the conjugation and proteasomal targeting of FAT10 are fairly well understood, the biological functions of FAT10 have remained largely elusive. Here we have investigated the role of FAT10 in cytokine responses in mice upon viral infection. We used lymphocytic choriomeningitis virus (LCMV) infection of mice to induce the IFN-γ and TNF-α-dependent expression of FAT10. We found that TCR-stimulated splenocytes derived from LCMV-infected FAT10&lt;sup&gt;-/-&lt;/sup&gt; mice secreted less IFN-γ and expressed less mRNA for IL-12 p40 but secreted more IFN-α and IFN-β compared to FAT10&lt;sup&gt;+/-&lt;/sup&gt; mice. The reduction in IFN-γ secretion could be assigned to CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Nevertheless, LCMV viral clearance was similar in FAT10&lt;sup&gt;-/-&lt;/sup&gt; as compared to FAT10&lt;sup&gt;+/-&lt;/sup&gt; mice. Since FAT10 has previously been reported to promote influenza A virus (IAV) replication in vitro we have studied the effect of FAT10 deficiency during IAV infection in mice. Unexpectedly, IAV titers and disease symptoms were not changed in FAT10&lt;sup&gt;-/-&lt;/sup&gt; mice even though the Fat10 mRNA was rapidly induced in the lung upon IAV infection. In conclusion, we find that FAT10 fine-tunes the balance of interferons during viral infection by lowering the production of type I and enhancing type II interferons.</dcterms:abstract>
    <dc:creator>Basler, Michael</dc:creator>
    <dc:creator>Gröttrup, Marcus</dc:creator>
    <dcterms:title>The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8&lt;sup&gt;+&lt;/sup&gt; T cells</dcterms:title>
    <dc:contributor>Basler, Michael</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:issued>2019-04</dcterms:issued>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-03-19T14:01:54Z</dc:date>
    <dc:contributor>Gröttrup, Marcus</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-03-19T14:01:54Z</dcterms:available>
    <dc:language>eng</dc:language>
    <dc:creator>Mah, Mei Min</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen