title: Decreased interleukin 27 expression is associated with active uveitis in Behçet's disease.
abstract: BACKGROUND
  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.
authors.forename: Chaokui
authors.initials: C
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D064094:Interleukin-27 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D014605:Uveitis / Q000097:blood / Q000235:genetics*; D055815:Young Adult; D000099185:Interferon Regulatory Factor-8
chemical_list: D017077:Culture Media, Conditioned; D050835:Interferon Regulatory Factors; D064094:Interleukin-27; D000099185:Interferon Regulatory Factor-8