Decreased interleukin 27 expression is associated with active uveitis in Behçet's disease.

Chaokui Wang,Aize Kijlstra,Yan Zhou,Peizeng Yang,Zi Ye,Yuan Tian

doi:10.1186/ar4570

Abstract

InstructionInterleukin 27 (IL-27) is an important regulator of the proinflammatory T-cell response. In this study, we investigated its role in the pathogenesis of Behçet’s disease (BD).MethodsIL-27 mRNA in peripheral blood mononuclear cells (PBMCs) was examined by performing RT-PCRs. Cytokine levels in sera or supernatants of PBMCs, naïve CD4+ T cells, dendritic cells (DCs) and DC/T cells were determined by enzyme-linked immunosorbent assay. We used RNA interference in naïve CD4+ T cells to study the role of interferon regulatory factor 8 (IRF8) in the inhibitory effect of IL-27 on Th17 cell differentiation. Flow cytometry was used to evaluate the frequency of IL-17- and interferon γ–producing T cells.ResultsThe expression of IL-27p28 mRNA by PBMCs and IL-27 in the sera and supernatants of cultured PBMCs were markedly decreased in patients with active BD. A higher frequency of IL-17-producing CD4+ T (Th17) cells and increased IL-17 production under Th17 polarizing conditions were observed in patients with active BD. IL-27 significantly inhibited Th17 cell differentiation. Downregulation of IRF8 by RNA interference abrogated the suppressive effect of IL-27 on Th17 differentiation. IL-27 inhibited the production of IL-1β, IL-6 and IL-23, but promoted IL-10 production, by DCs. IL-27-treated DCs inhibited both the Th1 and Th17 cell responses.ConclusionsThe results of the present study suggest that a decreased IL-27 expression is associated with disease activity in BD patients. Low IL-27 expression may result in a higher Th1 and Th17 cell response and thereby promote the autoinflammatory reaction observed in BD. Manipulation of IL-27 may offer a new treatment modality for this disease.

Highlights

Behçet’s disease (BD) is an autoinflammatory disease characterized by ocular, mucosal, skin and neurological lesions
Decreased expression of interleukin 27p28 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with active BD Interleukin 27 (IL-27) mRNA expression of the two subunits was analyzed in PBMCs obtained from patients with active BD, patients with inactive BD and healthy controls
Decreased levels of IL-27 in serum and in supernatants of cultured PBMCs from patients with active BD IL-27 levels were significantly lower in the serum from patients with active BD (955.5 ± 394.8 pg/ml) compared with patients with inactive BD (1,964.9 ± 1,885.8 pg/ml; P = 0.009) and healthy controls (2,608.9 ± 2,051.7 pg/ml; P < 0.001)

Summary

Introduction

Behçet’s disease (BD) is an autoinflammatory disease characterized by ocular, mucosal, skin and neurological lesions. It is one of the most common uveitis entities seen in the countries along the old Silk Road, such as Japan, Turkey, Israel and China [1,2]. Researchers in previous studies have shown that a type 1 T helper (Th1) cell response may play an important role in the pathogenesis of this disease. Researchers who have conducted studies in mice have reported that strategies aimed at suppressing the Th17 cell response were an effective therapeutic approach in experimental autoimmune uveitis (EAU), a mouse model of uveitis [9]

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