Role of Dendrtic Cells in IgA Nephropathy Pathogenesis

Zhi Xiao, Binbin Wang, Shu-fa Li
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Abstract

Objective to discuss the possible role and mechanism of DCs in IgAN attack. Method Stimulating factors such as recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), recombinant human interleukin-4 (rhIL-4) and tumor necrosis factor-a (TNF-a) etc. were used in vitro jointly to induce and culture DCs, a flow cytometry was used to detect expression of HLA-DR, CD83 and CDla of DCs membrane surface molecules, the MTT method was used to detect capacity of DCs of the IgAN patient group to stimulate proliferation of allogeneic T cells and the difference between the levels of interleukin 6 (IL-6) and interleukin 12 (IL-12) secreted by DCs and that of the normal control group. Result Combined application of cytokines GM-CSF, IL-4 and TNF-a is able to induce proliferation and differentiation of peripheral blood mononuclear cell into a mature dendritic cell. The surface of mature dendritic cells highly expresses human leucocyte antigen HLA-DR and surface maturity markers of relative specificity of dendritic cells, CD83 and CD1a. The capacity of DCs of the IgAN patient group to stimulate allogeneic T lymphocyte proliferation is higher than that of the normal control group and the difference has statistical significance (P<0.05). The capacity of DCs of the patient group influenced by lipopolysaccharide (LPS) to stimulate allogeneic T lymphocyte proliferation significantly increases compared with that of DCs of the patient group not influenced by lipopolysaccharide (LPS) and the difference has statistical significance (P<0.05). The IL-6 secreted by the DCs of the IgAN patient group is higher than that of the normal control group and the difference between the two groups has statistical significance (P<0.05). The IL-12 secreted by the DCs of the IgAN patient group is lower than that of the normal control group and the difference between the two groups has statistical significance (P<0.05). Conclusion DCs may regulate the balance between Thl/Th2 cells by secreting cytokines so as to play an imporat role in occurence and progression of IgAN and such factors as infection etc. may strengthen the functions of DCs thus easily triggering IgAN.
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树突状细胞在IgA肾病发病中的作用
目的探讨dc在IgAN发作中的可能作用及机制。方法采用重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)、重组人白细胞介素-4 (rhIL-4)、肿瘤坏死因子-a (TNF-a)等刺激因子体外联合诱导培养树突状细胞,采用流式细胞术检测树突状细胞膜表面分子HLA-DR、CD83、CDla的表达;MTT法检测IgAN患者组dc刺激异体T细胞增殖的能力及dc分泌的白细胞介素6 (IL-6)和白细胞介素12 (IL-12)水平与正常对照组的差异。结果GM-CSF、IL-4和TNF-a联合应用能诱导外周血单核细胞增殖分化为成熟的树突状细胞。成熟树突状细胞表面高度表达人白细胞抗原HLA-DR和树突状细胞相对特异性的表面成熟标志物CD83和CD1a。IgAN患者组dc对同种异体T淋巴细胞增殖的刺激能力高于正常对照组,差异有统计学意义(P<0.05)。受脂多糖(LPS)影响的患者组树突状细胞刺激同种异体T淋巴细胞增殖的能力较未受脂多糖(LPS)影响的患者组显著增高,差异有统计学意义(P<0.05)。IgAN患者组dc分泌的IL-6高于正常对照组,两组差异有统计学意义(P<0.05)。IgAN患者组dc分泌的IL-12低于正常对照组,两组差异有统计学意义(P<0.05)。结论dc可能通过分泌细胞因子调节Thl/Th2细胞间的平衡,在IgAN的发生和发展中起重要作用,感染等因素可增强dc的功能,容易触发IgAN。
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