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EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
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2018 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 4, p. 655-669Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 48, no 4, p. 655-669
Keywords [en]
4-1BB, CD4+ T cells, Cytotoxic T lymphocytes, Perforin-1, Rheumatoid Arthritis (RA)
National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-343246DOI: 10.1002/eji.201747296ISI: 000430105600012PubMedID: 29388193OAI: oai:DiVA.org:uu-343246DiVA, id: diva2:1185798
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-06-13Bibliographically approved

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Tandre, KarolinaRönnblom, Lars

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