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

Zana Brkic, Odilia B.J. Corneth, Cornelia G. van Helden-Meeuwsen, Radboud J.E.M. Dolhain, Naomi I. Maria, Sandra M.J. Paulissen, Nadine Davelaar, Jan P. van Hamburg, Paul L. van Daele, Virgil A. Dalm, P. M. van Hagen, Johanna M.W. Hazes, Marjan A. Versnel, Erik Lubberts

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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.

Original languageEnglish
Article numberR62
JournalArthritis Research and Therapy
Volume16
Issue number2
DOIs
Publication statusPublished - 6 Mar 2014

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