Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors
Mara Dittrich-Salamon,
Anja Meyer,
Shuaifeng Yan,
Eva Steinbach-Knödgen,
Konstantin Kotschenreuther,
David Stahl,
Carola tho Pesch,
Joanna Schiller,
Franziska Byrtus,
Dorothee Jochimsen,
Viktoria Golumba-Nagy,
David M. Kofler
Affiliations
Mara Dittrich-Salamon
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Anja Meyer
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Shuaifeng Yan
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Eva Steinbach-Knödgen
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Konstantin Kotschenreuther
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
David Stahl
Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Carola tho Pesch
Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Joanna Schiller
Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Franziska Byrtus
Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Dorothee Jochimsen
Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Viktoria Golumba-Nagy
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
David M. Kofler
Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Regulatory T (Treg) cells play an important role in immune tolerance and contribute to the prevention of autoimmune diseases, including rheumatoid arthritis (RA). The differentiation, function and stability of Treg cells is controlled by members of the Ikaros zinc finger transcription factor family. In this study, we aimed to reveal how the expression of Ikaros transcription factors is affected by disease activity in RA. Therefore, we analyzed the ex vivo expression of Ikaros, Helios, Aiolos and Eos in Treg cells, Th17 cells and Th1 cells from RA patients by flow cytometry. We found significantly reduced expression of Helios, Aiolos and Eos in Treg cells from RA patients as compared to healthy controls. Moreover, Helios and Aiolos levels correlated with disease activity, as assessed by DAS28-CRP. In addition, Ikaros, Helios and Aiolos were significantly downregulated in Th1 cells from RA patients, while no difference between healthy individuals and RA was observed in Th17 cells. In summary, Helios and Aiolos expression in Treg cells correlates with disease activity and the expression levels of Ikaros transcription factors are diminished in Treg cells from RA patients. This observation could explain the reduced stability of Treg cells in RA.
