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EOMES-positive CD4+...
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Chemin, KarineKarolinska Institutet
(författare)
EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
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2018-02-28
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Wiley,2018
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-343246
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-343246URI
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https://doi.org/10.1002/eji.201747296DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:138038104URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4+ T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation. Moreover, the protein expression of the T-box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4+ T cells. There was no difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES+CD4+ T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4+ T cells and identify EOMES+CD4+ T cells as a relevant T-cell subset in RA pathogenesis.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Ramsköld, DanielKarolinska Institutet
(författare)
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Diaz-Gallo, Lina-MarcelaKarolinska Institutet
(författare)
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Herrath, JessicaRheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
(författare)
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Houtman, MirandaKarolinska Institutet
(författare)
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Tandre, KarolinaUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karotand
(författare)
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Rönnblom, LarsUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)larsronn
(författare)
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Catrina, AncaKarolinska Institutet
(författare)
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Malmström, VivianneKarolinska Institutet
(författare)
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Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:European Journal of Immunology: Wiley48:4, s. 655-6690014-29801521-4141
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