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Arthritis Research and Therapy

, 16:R117

First Online: 28 May 2014Received: 09 October 2013Accepted: 07 May 2014

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.

AbbreviationsAPCAntigen-presenting cell

BDBehçet’s disease

DCDendritic cell

EAEExperimental autoimmune encephalomyelitis

EAUExperimental autoimmune uveitis

EBI3Epstein–Barr virus-induced gene 3

ILInterleukin

IRF8Interferon regulatory factor 8

STAT1Signal transducer and activator of transcription 1

Tr1Type 1 regulatory T cell.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4570 contains supplementary material, which is available to authorized users.

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Author: Chaokui Wang - Yuan Tian - Zi Ye - Aize Kijlstra - Yan Zhou - Peizeng Yang

Source: https://link.springer.com/



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