Dendritic cell activation mechanisms by nucleic by nucleic acid immune adjuvants.

树突状细胞（dc）通过toll样受体（TLRs）识别多种核酸，并产生促炎细胞因子或I型干扰素（ifn）。在这项研究中，我们分析了这些DC功能的潜在分子机制。在tlr中，TLR3、TLR7和TLR9参与核酸识别。其中一个DC亚群浆细胞样DC （plasmacytoid DC, pDC）在tlr中只表达TLR7和TLR9，并在TLR7/9刺激下产生大量I型ifn。一种丝氨酸苏氨酸激酶，IkB激酶α (IKKα)，在tlr7 /9刺激的pDC产生I型IFN的过程中起关键作用。IKKα运作。通过与转录因子IRF-7的关联和磷酸化，已知IRF-7对TLR7/9刺激产生I型IFN至关重要。我们进一步研究了双链RNA poly （a: U）激活dc的机制。Poly （I: C）是一种众所周知的双链RNA，它可以通过TLR3和胞质传感器RIG-Hike受体（RLR）激活DCs，但Poly （a: U）如何激活DCs仍不清楚。Poly （A: U）激活pDC以依赖tlr7的方式产生I型IFN和IL-12p40。Poly （A: U）也可以通过TLR3和TLR7诱导常规DC （cDC）中的IL-12p40。当与抗原（Ag）一起注射到小鼠体内时，poly （A: U）可以诱导Ag特异性cd8阳性T细胞的克隆扩增和IFN-y的产生。TLR3主要参与poly （A: U）的这些体内效应。因此，poly （A: U）可以通过TLR3和TLR7发挥免疫佐剂的作用。

Dendritic cells (DCs) recognize a variety of nucleic acids through Toll-like receptors (TLRs) and produce proinflammatory cytokines or type I interferons (IFNs). In this study, we have analyzed the underlying molecular mechanisms on these DC functions. Among TLRs, TLR3, TLR7 and TLR9 are involved in nucleic acid recognition. One DC subset, plasmacytoid DC (pDC), expresses TLR7 and TLR9 exclusively among TLRs and produce a large amount of type I IFNs upon TLR7/9 stimulation. A serine threonine kinase, IkB kinase α (IKKα), is critically involved in type I IFN production from TLR7/9-stimulated pDC. IKKα functioned. through the association with and phosphorylation of a transcription factor, IRF-7, which was known to be critical for type I IFN production by TLR7/9 stimuli. We have further investigated the mechanism by which a double-stranded RNA, poly (A: U) activate DCs. Poly (I: C) is a well-known double-stranded RNA, which can activate DCs through TLR3 and a cytosolic sensor, RIG-Hike receptor (RLR), but it remained unknown how poly (A: U) activates DCs. Poly (A: U) activated pDC to produce type I IFN and IL-12p40 in a TLR7-dependent manner. Poly (A: U) also induced IL-12p40 from conventional DC (cDC) through TLR3 and TLR7. When injected with antigen (Ag) into mice, poly (A: U) could induce clonal expansion of and IFN-y production from Ag-specific CD8-positive T cells. TLR3 was mainly involved in these in vivo effects of poly (A: U). Thus, poly (A: U) can function as an immune adjuvant through TLR3 and TLR7.