Interferon-alpha2a induces CD4(+) T cell apoptosis and suppresses Th1/Th17 responses via upregulating IRF1-mediated PDL1 expression in dendritic cells from Behcet's uveitis.

Recombinant interferon-alpha2a (IFNalpha2a) has been widely used in the treatment of Behcet's uveitis (BU). However, the mechanism underlying its effects remains poorly understood. In this study, we investigated its effect on dendritic cells (DCs) and CD4(+) T cells, which are essential for the development of BU. Our results showed that the expression of PDL1 and IRF1 was significantly decreased in DCs from active BU patients, and IFNalpha2a could significantly upregulate PDL1 expression in an IRF1-dependent manner. IFNalpha2a-treated DCs induced CD4(+) T cells apoptosis and inhibited the Th1/Th17 immune response in association with reduced secretion of IFN-gamma and IL-17. We also found that IFNalpha2a promoted Th1 cell differentiation and IL-10 secretion by CD4(+) T cells. Finally, a comparison of patients before and after IFNalpha2a therapy revealed that the frequencies of Th1/Th17 cells significantly decreased in association with remission of uveitis after IFNalpha2a therapy. Collectively, these results show that IFNalpha2a could exert its effects by modulating the function of DCs and CD4(+) T cells in BU.