Dendritic cell subsets and type I interferon system in Behçet's disease: does functional abnormality in plasmacytoid dendritic cells contribute to Th1 polarization?

Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). However, it is not yet clear which factors are involved in the proposed Th1 mediated pathogenesis of BD. Dendritic cells (DCs) are antigen presenting cells which play a crucial role in the polarization of immune response. No previous study has examined the possible role of DCs in the pathogenesis of BD. We conducted both quantitative and functional analysis of the peripheral blood DC subsets in BD patients with different clinical presentations.Thirty-eight patients with BD, 12 healthy controls (HC), and 12 patients with undifferentiated spondylarthritis (uSpA) were enrolled in the study. Peripheral blood DC subsets were analysed by flow cytometry and were further characterized for maturation with CCR7. Serum levels of interferon (IFN)-alpha and IFN-b were measured by ELISA.BD patients had a decreased percentage of plasmacytoid DCs (pDCs) compared to HC (p = 0.036). IFN-alpha levels were found to be increased in BD patients as compared to HC and uSPA (p < 0.001, p = 0.005, respectively). BD patients had decreased levels of IFN-Beta as compared to HC and uSpA (p = 0.013, p = 0.004, respectively). No difference was found between HC and patients with uSpA regarding IFN-Beta levels. Subgroup analysis of BD patients disclosed normalization of percentage of pDCs and the level of IFN-Beta in patients receiving IFN-alpha-2b.We suggest abnormalities in pDCs and type I IFNs appear to be a master switch leading to the pathogenicity in BD by directing immune response towards Th1.