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EOMES-positive CD4+...
EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.
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- Chemin, Karine (author)
- Karolinska Institutet
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- Ramsköld, Daniel (author)
- Karolinska Institutet
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- Diaz-Gallo, Lina-Marcela (author)
- Karolinska Institutet
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- Herrath, Jessica (author)
- Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden
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- Houtman, Miranda (author)
- Karolinska Institutet
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- Tandre, Karolina (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Catrina, Anca (author)
- Karolinska Institutet
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- Malmström, Vivianne (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2018-02-28
- 2018
- English.
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 48:4, s. 655-669
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- 4-1BB
- CD4+ T cells
- Cytotoxic T lymphocytes
- Perforin-1
- Rheumatoid Arthritis (RA)
- Medicinsk vetenskap
- Medical Science
Publication and Content Type
- ref (subject category)
- art (subject category)
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