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Peizeng Yang, Chaokui Wang, Yuan Tian, Zi Ye, Aize Kijlstra; Decreased Interleukin-27 Expression is Associated with Active Uveitis in Behcet’s Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6905.
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IL-27 is an important regulator of the proinflammatory T cell response. In this study, we investigated its role in the pathogenesis of Behcet’s disease (BD).
IL-27 mRNA expression in peripheral blood mononuclear cells (PBMCs) from active BD patients, inactive BD patients and normal controls was examined using RT-PCR. Cytokine levels in serum or supernatants of cultured PBMCs, naïve CD4+T cells, DCs and DC/T cells were determined by ELISA. RNA interference was performed in naïve CD4+T cells to study the role of IRF-8 in the inhibitory effect on Th17 cell differentiation. Flow cytometry was used to evaluate the frequency of IL-17- and IFN-γ-producing T cells. AAV2-mediated subretinal gene transfer of mIL-27 was performed to evaluate its effect on experimental autoimmune uveitis (EAU) and cytokine production in mice.
The expression of IL-27P28 mRNA by PBMCs and IL-27 in the serum and supernatants of cultured PBMCs were markedly decreased in active BD patients as compared to inactive BD patients and normal controls. A higher frequency of IL-17-producing CD4+T cells and an increased IL-17 production under Th17 polarizing conditions was observed in active BD patients. IL-27 significantly inhibited Th17 cell differentiation. It inhibited the production of IL-1β, IL-6 and IL-23, but promoted IL-10 production by DCs. IL-27-treated DC inhibited both the Th1 and Th17 cell response. Downregulation of IRF-8 by RNA interference significantly interfered the suppressive effect of IL-27 on Th17 differentiation. Subretinal injection of AAV2-CMV-mIL-27 vector could induce a high and stable IL-27 expression within the eye and significantly attenuate EAU activity in association with a decreased IL-17 expression and an increased IL-10 expression.
The present results suggest that a decreased IL-27 expression is associated with active disease activity in BD patients. IL-27 inhibits Th17 cell response possibly through modulating IRF-8. Manipulation of IL-27 may offer a new treatment modality for this disease.
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