Expression of Th17 and related cytokines according to clinical activity of Behcet's disease

Abstract

Background: Behçet’s disease (BD) is a multisystem inflammatory disorder characterized by recurrent oro-genital ulcers, and cutaneous, ocular, arthritics, gastrointestinal, vascular, and neurovascular involvement. The etiology and pathogenesis of BD have remained unclear, however it has been assumed that genetic factors, infectious, and immune mechanisms are involved in the onset of this disease. In human autoimmunity, the T helper(Th) 1 immune responses have been traditionally associated with the induction and progression of disease. Recently, a number of other T cell populations were discovered, and IL(Interleukin)-17 producing Th17 cells were recognized as novel group of T cells which play a major role in autoimmunity. A recent study has shown elevated production of IL-17, IL-23, and IFN (Interferon)-γ by peripheral blood mononuclear cells (PBMCs) besides increased frequencies of IL-17 and IFN-γ producing T cells in BD patients with active uveitis. It was also reported that increased expression of IL-23 p19 mRNA in erythema nodosum-like lesions in patients with active BD.

Purpose: In this study, we aimed at investigating the expression Th17 and related cytokines during active states of BD.

Materials and Methods: From April 2010 to September 2010, a total of 22 patients with active and inactive BD were enrolled in this study. The disease control and healthy control (HC) group consisted of age- and sex-matched 10 recurrent aphthous ulcer (RAU) patients without any other evident disease and 10 healthy volunteers, respectively. PBMCs of subjects were cultured and stained with the appropriate fluorescent antibody for analysis by flow cytometry. To measure the IL-17, IL-23 and IFN-γ concentrations in serum and in culture supernatants, ELISA was performed. To investigate the mRNA expression level of IL-12p35, IL-12/23p40 and IL-23p19 in PBMCs, real time polymerase chain reaction (RT-PCR) was performed.

Results: In the active BD group, CD4+ and CD8+ T cells from patients expressed significantly higher level of IL-17 and IFN-γ, compared with the cells from the control group. High serum and supernatant concentration of IL-17 and IFN-γ was in active BD group compared with HC group and RAU group. In addition, mRNA expression of IL-23p19, IL-12p35 and IL-12/23p40 in PBMCs was up-regulated in total BD patient groups. Expression of IL-23p19 mRNA was significantly higher in the active BD group compared with HC groups.

Conclusion: Increased expression of the IL-17 and IFN-γ was observed in this study and these results suggest that Th17 cells has a important implication in immune modulation of BD. Future studies clarifying the further immunopathologic role of Th17 pathway in BD are needed.