Format

Send to

Choose Destination
Eur J Immunol. 2018 Apr;48(4):655-669. doi: 10.1002/eji.201747296. Epub 2018 Feb 28.

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

Author information

1
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
2
Department of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Abstract

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.

KEYWORDS:

4-1BB; CD4+ T cells; Perforin-1; Rheumatoid Arthritis (RA); cytotoxic T lymphocytes

PMID:
29388193
DOI:
10.1002/eji.201747296
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center