{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:58:59Z","timestamp":1790834339456,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T00:00:00Z","timestamp":1519776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC grant number 260167"],"award-info":[{"award-number":["ERC grant number 260167"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The presence of the <jats:italic>PTPN22<\/jats:italic> risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of <jats:italic>PTPN22<\/jats:italic> in T\u00a0cells, the exact impact of the <jats:italic>PTPN22<\/jats:italic> risk allele on T\u2010cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR\u2010activation, na\u00efve human CD4<jats:sup>+<\/jats:sup> T\u00a0cells homozygous for the <jats:italic>PTPN22<\/jats:italic> risk allele overexpress a set of genes including <jats:italic>CFLAR<\/jats:italic> and <jats:italic>4\u20101BB<\/jats:italic>, which are important for cytotoxic T\u2010cell differentiation. Moreover, the protein expression of the T\u2010box transcription factor Eomesodermin (EOMES) was increased in T\u00a0cells from healthy donors homozygous for the <jats:italic>PTPN22<\/jats:italic> risk allele and correlated with a decreased number of na\u00efve CD4<jats:sup>+<\/jats:sup> T\u00a0cells. There was no difference in the frequency of other CD4<jats:sup>+<\/jats:sup> T\u2010cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T\u00a0cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin\u20101 in <jats:italic>PTPN22<\/jats:italic> risk allele carriers. Altogether, we propose a novel mechanism of action of <jats:italic>PTPN22<\/jats:italic> risk allele through the generation of cytotoxic CD4<jats:sup>+<\/jats:sup> T\u00a0cells and identify EOMES<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T\u00a0cells as a relevant T\u2010cell subset in RA pathogenesis.<\/jats:p>","DOI":"10.1002\/eji.201747296","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T03:22:43Z","timestamp":1517455363000},"page":"655-669","source":"Crossref","is-referenced-by-count":42,"title":["EOMES\u2010positive CD4<sup>+<\/sup> T\u00a0cells are increased in <i>PTPN22<\/i> (1858T) risk allele carriers"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2597-7809","authenticated-orcid":false,"given":"Karine","family":"Chemin","sequence":"first","affiliation":[{"name":"Rheumatology Unit Department of Medicine Karolinska University Hospital Solna Karolinska Institute  Stockholm 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