Expression Of Toll-like Receptor7and9in The Peripheral Blood Plasmacytoid Dendritic Cells Of Patients With Chronic Myeloid Leukemia

Objective: Chronic myeloid leukemia (CML) is a malignant proliferation disease of hematop-oieticc stem cell. In recent years, with the deep research of immune pathogenesis of CML, immun-otherapy has been focused on CML therapy, especially on the areas of minimal residual disease. Plasmacytoid dendritic cells (pDCs) play a pivotal role in linking innate and adaptive immune responses. pDCs are a unique subset capable of secreting high levels of interferon-a (IFN-a), and IFN-a is very important in the treatment of CML. Many researchs have confirmed that the pDCs come from CML patients were defective in number and function, but the cause of function defects is still not clear. Toll-like receptor7and9are the important pattern recognition receptors on pDCs, and participate in mediation of IFN-a production. This study aims to investigate the expression of TLR7and TLR9mRNA in the peripheral blood pDCs of patients with CML, and the function of pDCs secretion IFN-α. Discusses the main reason of function defects of pDCs, further describe the role of TLR7and TLR9in CML, provide the basis for CML immunotherapy.Methods: Peripheral blood mononudear cells (PBMCs) from CML patients in chronic phase at diagnosis, remission phase and healthy controls were isolated by density gradient centrifugation, pDCs were sorted by immune magnetic beads from PBMCs, pDCs were stimulated by CpG ODN2216for24h in vitro, IFN-a in the supernatant was measured using enzyme-linked iminuno-sorbent assay(ELISA); the mRNA of TLR7and TLR9of pDCs were measured with Real time-PCR.Results: The ability of pDCs to secrete IFN-a was significantly reduced from CML untreated group(408.61±77.11) ng/L than that in healthy controlsf (651.67±93.39) ng/L](P<0.05), compared to the untreated group, the remission group (611.39±84.86) ng/L was significantly increased (P<0.05), but was still less than healthy controls(P>0.05). The expression of TLR7mRNA and TLR9mRNA on pDCs were significantly reduced from CML untreated groupf (0.34±0.11),(0.44±0.15)] than healthy controls (P<0.05); compared to the untreated group, the remission group[(0.93±0.21),(0.94±0.18)]\vas significantly increased (P<0.05), but was still less than healthy controlsfT^O.OS).Conclusion: The expression of TLR7mRNA and TLR9mRNA on pDCs were significantly reduced from CML untreated group, it is the main reason of function defects of pDCs, involved in the pathogenesis of CML.