The Role Of Plasmacytoid Dendritic Cells And Their Toll-like Receptor9in The Pathogenesis Of Immune Thrombocytopenia

Objective:Immune thrombocytopenia (ITP) belongs to an autoimmune disease and is involved in the humoral and cellular immune dysfunction. The pathogenesis of ITP are not obvious. Plasmacytoid dendritic cells (pDCs) depending on Toll-like receptor9(TLR9) identify a variety of bacterial or viral CpG motif, and then secrete large amounts of interferon (IFN-a) and inflammatory cytokines (IL-6and TNF-α). It is not only the key to start the innate immune response, but also the bridge between innate and adaptive immune bridges, playing an important role in the immune system. High-dose dexamethasone (HD-DEX) pulse therapy because of its significant effect. has become the first-line treatment of ITP, but the impact on pDCs function of its TLR9expression is not clear. In this study, aim to investigate the function of pDCs secrete cytokines and the expression of TLR9mRNA in the peripheral blood pDCs of patients with ITP. To explore the role of plasmacytoid dendritic cells functions and TLR9expression in the pathogenesis of ITP, further to elaborated in the HD-DEX targets of ITP treatment.Methods:The peripheral blood mononuclear cells (PMNCs) from13patients before and after treatment of HD-DEX and15healthy controls were isolated by density gradient centrifugation, pDCs were sorted by immune magnetic beads from PMNCs. pDCs were induced by CpG-OND2216for24hours in vitro, the levels of IFN-α, IL-6and TNF-a in the supernatant were detected by enzyme linked immunosorbent assay (ELISA). The expression of TLR9mRNA of pDCs was detected by Real-time quantitative PCR (RT-PCR).Results:The ability of pDCs to secrete IFN-a, IL-6and TNF-a is significantly increasing in ITP patients before treatment [(960.83±164.65)pg/ml,(156.15±39.89) pg/ml,(137.31±35.44)pg/ml)] as compared with that in healthy controls [(616.67±105.98)pg/ml,(89.13±21.48)pg/ml,(88.53±25.81)pg/ml)](P<0.05). After HD-DXM treatment, the levels of IFN-a, IL-6and TNF-a [(678.46±128.88)pg/ml,(97.77±26.31)pg/ml,(103.08±26.42)pg/ml] were decreased significantly without statistics significance between HD-DXM treatment patients and healthy controls (P>0.05). The expression of TLR9mRNA in pDCs of group untreated were significantly higher than group treated and healthy controls (P<0.05). TLR9mRNA level in pDCs of group treated was significantly reduced, being no difference from that in healthy controls (P>0.05).Conclusion:PDCs may play an important role in ITP by their Toll-like receptor9and cytokines secretion; dexamethasone may be reduced by the expression of TLR9, inhibit pDC function, and playing a therapeutic role.