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

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.

SUBMITTER: Brkic Z 

PROVIDER: S-EPMC4060204 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature