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Open Access Highly Accessed Research article

T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Zana Brkic1, Odilia BJ Corneth12, Cornelia G van Helden-Meeuwsen1, Radboud JEM Dolhain2, Naomi I Maria1, Sandra MJ Paulissen12, Nadine Davelaar12, Jan Piet van Hamburg12, Paul L van Daele1, Virgil A Dalm1, P Martin van Hagen1, Johanna MW Hazes2, Marjan A Versnel1 and Erik Lubberts12*

Author Affiliations

1 Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, P.O. Box 1738, Rotterdam 3000 DR, The Netherlands

2 Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, P.O. Box 1738, Rotterdam 3000 DR, The Netherlands

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Arthritis Research & Therapy 2014, 16:R62  doi:10.1186/ar4499

Published: 6 March 2014

Abstract

Introduction

A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6+ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.

Methods

In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN+) (n = 16) and negative (IFN-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4+CD45RO+CCR6+ T cells (CCR6+ cells) was measured with flow cytometry and compared between IFN+, IFN- patients and HCs.

Results

Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ cells were observed in IFN+ patients compared with IFN- patients and HCs. IL-17A and IL-17F expression within CCR6+ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6+ cells.

Conclusions

We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ memory T-helper cells in IFN+ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.