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

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

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8 Citations (Scopus)

Abstract

INSTRUCTION: Interleukin 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).

METHODS: IL-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.

RESULTS: The 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.

CONCLUSIONS: The 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.

Original languageEnglish
Article numberR117
JournalArthritis Research & Therapy
Volume16
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Adult
  • Behcet Syndrome
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Cells, Cultured
  • Culture Media, Conditioned
  • Dendritic Cells
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Interferon Regulatory Factors
  • Interleukin-27
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th17 Cells
  • Uveitis
  • Young Adult

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