EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.

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.

Ramsköld, DanielKarolinska Institutet (författare)
Diaz-Gallo, Lina-MarcelaKarolinska Institutet (författare)
Herrath, JessicaRheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden (författare)
Houtman, MirandaKarolinska Institutet (författare)
Tandre, KarolinaUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)karotand (författare)
Rönnblom, LarsUppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)larsronn (författare)
Catrina, AncaKarolinska Institutet (författare)
Malmström, VivianneKarolinska Institutet (författare)
Karolinska InstitutetRheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden (creator_code:org_t)

Av författaren/redakt...: Chemin, Karine; Ramsköld, Daniel; Diaz-Gallo, Lina ...; Herrath, Jessica; Houtman, Miranda; Tandre, Karolina; visa fler...; Rönnblom, Lars; Catrina, Anca; Malmström, Vivia ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Reumatologi och ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.