BDCA2对CpG ODN激活的浆细胞样树突状细胞（pDCs）的负相调控作用

发布时间：2018-06-22 22:07

本文选题：浆细胞样树突状细胞 + BDCA2　；参考：《浙江大学》2005年硕士论文

【摘要】：Ⅰ型干扰素产生细胞(Type 1 interferon producing cells,IPCs)又称为浆细胞样树突状细胞前体(plasmacytoid dendritic cell precursors,pDCs),代表一类占外周血单核细胞的0.2%-0.8%、表型为CD123~(high)CD4~+CD11c~-Lin~-(CD3,CD14,CD16,CD19,CD56)的特异性细胞亚群。与以往的树突状细胞不同,pDCs在形态上表面光滑、圆形类似于淋巴细胞样;在TLR受体表达上,单核细胞表达TLR1、2、4、5、6、8,髓系树突状细胞(mDC)表达TLR3,而pDCs则表达单链病毒RNA配体TLR7和DNA病毒及CpG寡聚脱氧核苷酸(CpG ODN)的配体TLR9,从而决定了他们对不同抗原的应答类型和强度;pDCs的一个突出特征是在病毒、CpGODN刺激下可以迅速分泌大量的Ⅰ型干扰素,从而发挥抗病毒效应,并在抗病毒免疫应答中进一步促进NK细胞、B细胞、T细胞和髓系树突状细胞的作用。同时pDCs在自身分泌的Ⅰ型干扰素和TNF-α等细胞因子的作用下向成熟DC分化。因此,pDCs在机体抵抗病毒感染,以及在自身免疫性疾病及肿瘤的发生发展方面发挥着重要的免疫调控作用。 BDCA2是一类含有213个氨基酸的新的二型跨膜糖蛋白,属于钙依赖性凝集素家族。BDCA2是pDCs的特异性表面分子,在外周血和骨髓中无一例外地表达于Lin~-CD4~(di)~mCD123~(bright)CD11c~-CD45RA~+ BDCA-1~-BDCA-3~(dim)的pDCs,同时在骨髓中,一小群细胞亦表达较低水平的BDCA2,该群CD34~(dim)CD45RA~(dim)BDCA-2~(dim)细胞直接来源于CD34~(bright) CD45RA-BDCA-2-定向造血干细胞(hematopoietic progenitor cells,HPCs),被认为是pDCs的前体细胞。尽管BDCA-2胞浆区缺乏已知的信号基序,但目前认为BDCA-2是一类信号受体。用抗BDCA-2的单克隆抗体AC144作用于靶细胞以激活BDCA2,可致src家族蛋白酪氨酸激酶依赖的胞浆区钙的内移,并使胞内蛋白的酪氨酸磷酸化。此外,pDCs还可有效地呈递该抗原至T细胞。因此,BDCA2被认为可介导内吞。但是否BDCA2具有捕获抗原的生理学作用仍待进一步研究。
[Abstract]:Type I interferon producing cells (Type 1 interferon producing cells, IPCs) are also known as plasma cell like dendritic cell precursors (plasmacytoid dendritic cell precursors, pDCs), representing a class of specific cell subgroups that occupy peripheral blood mononuclear cells. In different dendritic cells, pDCs is smooth in morphology and round like lymphocyte like; in the expression of TLR receptor, monocytes express TLR1,2,4,5,6,8, myeloid dendritic cells (mDC) express TLR3, while pDCs expresses the ligand TLR7 of the single chain virus RNA ligand and DNA virus and CpG oligo deoxynucleotide (CpG ODN). The type and intensity of their response to different antigens; one of the prominent features of pDCs is that a large number of type I interferons can be secreted rapidly under the stimulation of the virus and CpGODN, which plays an antiviral effect and further promotes the role of NK cells, B cells, T cells and myeloid dendritic cells in the antiviral immune response. And pDCs is secreted in its own secretion. The cell factor of type I interferon and TNF- alpha differentiates into the mature DC. Therefore, pDCs plays an important role in immune regulation in the body against virus infection and in the development of autoimmune diseases and tumor.
BDCA2 is a class of new type two transmembrane glycoproteins containing 213 amino acids, which belong to the calcium dependent lectin family.BDCA2, a specific surface molecule of pDCs. There is no case in the peripheral blood and bone marrow of the Lin~-CD4~ (DI) ~mCD123~ (bright) CD11c~-CD45RA~+ BDCA-1~ -BDCA-3~ (DIM) pDCs, and a small group of cells in the bone marrow are also table. At a lower level of BDCA2, the group of CD34~ (DIM) CD45RA~ (DIM) BDCA-2~ (DIM) cells directly originate from CD34~ (bright) CD45RA-BDCA-2- directed hematopoietic stem cells (hematopoietic progenitor).
Cells, HPCs) is considered to be a precursor of pDCs. Although the BDCA-2 cytoplasm area lacks known signal motif, BDCA-2 is currently considered as a class of signal receptors. The anti BDCA-2 monoclonal antibody AC144 acts on the target cells to activate BDCA2, causing the intracellular calcium of the Src family protein tyrosine kinase in the cytosol region and the casein of the intracellular protein. In addition, pDCs can also effectively deliver the antigen to T cells. Therefore, BDCA2 is considered to mediate endocytosis. But whether BDCA2 has a physiological role to capture antigen remains to be further studied.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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