Open Access Research article

Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus

Sebastian Dolff12*, Wayel H Abdulahad1, Johanna Westra1, Berber Doornbos-van der Meer1, Pieter C Limburg1, Cees GM Kallenberg1 and Marc Bijl1

Author Affiliations

1 Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands

2 Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany

For all author emails, please log on.

Arthritis Research & Therapy 2011, 13:R157  doi:10.1186/ar3474

Published: 29 September 2011

Abstract

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients.

Methods

Peripheral blood of 34 SLE patients and 18 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore (Ca-Io). Percentages of IL-21- and IL-17A expressing T-cells were analysed by flow cytometry. The expression levels of the transcription factors B-cell lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-γt) were assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21 receptor (IL-21R) expression on B- and T-cells of patients and HC was analyzed.

Results

Significantly increased percentages of IL-21 expressing CD4+ T-cells and CD8+ T-cells were found in SLE patients as compared to HC. The percentages of IL-21+ CD4+ T-cells and CD8+ T-cells correlated significantly with the percentages of IL-17A+ CD4+ T-cells and CD8+ T-cells, respectively. The relative expression of BCL-6 and ROR-γt did not differ between SLE patients and HC. IL-21R expression occurred mainly on B-cells and was not different comparing SLE patients and HC.

Conclusions

This study demonstrates an increased proportion of IL-21+ T-cells in SLE patients correlating with the proportion of IL-17+ T-cells. This suggests a pivotal role of IL-21 in the pathogenesis of SLE.

Keywords:
SLE; Th17-cells; IL-21; T-cells