Toll-like receptor-dependent immune complex activation of B cells and dendritic cells.
Toll-like receptor-dependent immune complex activation of B cells and dendritic cells.
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Toll 样受体依赖性免疫复合物激活 B 细胞和树突状细胞。
DOI：
10.1007/978-1-59745-541-1_22
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Viglianti,GregoryA
中科院分区：
文献类型：
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作者：
Uccellini,MelissaB;Avalos,AnaM;Marshak-Rothstein,Ann;Viglianti,GregoryA
与 DNA/RNA 分子复合物发生反应的高滴度自身抗体是系统性红斑狼疮 (SLE) 等自身免疫性疾病的特征。体外和体内研究表明 Toll 样受体 9 (TLR9) 和 Toll 样受体 7 (TLR7) 参与相应自身抗体产生 B 细胞的激活。重要的是，TLR9/TLR7 缺陷导致自身反应性 B 细胞无法在体外对 DNA/RNA 相关自身抗原作出反应而增殖，并导致易患自身免疫的小鼠的自身抗体库发生显着变化。 DNA/RNA 相关自身抗原免疫复合物 (IC) 的摄取也会通过 TLR9 和 TLR7 激活树突状细胞 (DC)。我们实验室的初步研究涉及由自身抗体和培养中垂死细胞释放的细胞碎片混合物形成的 IC。为了更好地了解能够有效激活 TLR7 和 TLR9 的哺乳动物配体的性质，我们开发了一种制备包含特定 DNA 片段的 IC 的方法，该片段概括了之前“黑匣子”IC 的免疫刺激活性。这些试剂揭示了核酸序列的重要作用，即使配体是哺乳动物 DNA。
High titers of autoantibodies reactive with DNA/RNA molecular complexes are characteristic of autoimmune disorders such as systemic lupus erythematosus (SLE). In vitro and in vivo studies have implicated Toll-like receptor 9 (TLR9) and Toll-like receptor 7 (TLR7) in the activation of the corresponding autoantibody producing B cells. Importantly, TLR9/TLR7-deficiency results in the inability of autoreactive B cells to proliferate in response to DNA/RNA-associated autoantigens in vitro, and in marked changes in the autoantibody repertoire of autoimmune-prone mice. Uptake of DNA/RNA-associated autoantigen immune complexes (ICs) also leads to activation of dendritic cells (DCs) through TLR9 and TLR7.The initial studies from our lab involved ICs formed by a mixture of autoantibodies and cell debris released from dying cells in culture. To better understand the nature of the mammalian ligands that can effectively activate TLR7 and TLR9, we have developed a methodology for preparing ICs containing defined DNA fragments that recapitulate the immunostimulatory activity of the previous “black box” ICs. These reagents reveal an important role for nucleic acid sequence, even when the ligand is mammalian DNA.