PDF(Pubmed)
Abstract：
Small synthetic oligodeoxynucleotides (ODNs) can mimic microbial nucleic acids by interacting with receptor systems and promoting immunostimulatory activities. Nevertheless, some ODNs can act differently on the plasmacytoid dendritic cell (pDC) subset, shaping their immunoregulatory properties and rendering them suitable immunotherapeutic tools in several clinical settings for treating overwhelming immune responses. We designed HIV-1-derived, DNA- and RNA-based oligonucleotides (gag, pol, and U5 regions) and assessed their activity in conferring a tolerogenic phenotype to pDCs in skin test experiments. RNA-but not DNA-oligonucleotides are capable of inducing tolerogenic features in pDCs. Interestingly, sensing the HIV-1-derived single-stranded RNA-gag oligonucleotide (RNA-gag) requires both TLR3 and TLR7 and the engagement of the TRIF adaptor molecule. Moreover, the induction of a suppressive phenotype in pDCs by RNA-gag is contingent upon the induction and activation of the immunosuppressive enzyme Arginase 1. Thus, our data suggest that sensing of the synthetic RNA-gag oligonucleotide in pDCs can induce a suppressive phenotype in pDCs, a property rendering RNA-gag a potential tool for therapeutic strategies in allergies and autoimmune diseases.
摘要：
小合成寡脱氧核苷酸（ODN）可以通过与受体系统相互作用并促进免疫刺激活性来模拟微生物核酸。然而，一些ODN可以对浆细胞样树突状细胞（pDC）亚群起不同的作用，塑造它们的免疫调节特性，并在几种临床环境中为它们提供合适的免疫治疗工具，以治疗压倒性的免疫反应。我们设计了HIV-1衍生的,基于DNA和RNA的寡核苷酸(gag，波尔,和U5区域），并评估了它们在皮肤测试实验中赋予pDC耐受原表型的活性。RNA-但不是DNA-寡核苷酸能够在pDC中诱导致耐受性特征。有趣的是,检测HIV-1衍生的单链RNA-gag寡核苷酸(RNA-gag)需要TLR3和TLR7以及TRIF衔接分子的接合.此外，通过RNA-gag在pDC中诱导抑制性表型取决于免疫抑制酶精氨酸酶1的诱导和激活。因此，我们的数据表明，pDCs中合成RNA-gag寡核苷酸的感知可以诱导pDCs中的抑制性表型，使RNA-gag成为过敏和自身免疫性疾病治疗策略的潜在工具。
