人类细胞含有两种类型的腺苷脱氨酶 (ADA)，每种都具有独特的特性：ADA1 存在于所有细胞中，调节细胞内功能和细胞外信号传导；ADA2 由免疫细胞分泌。 ADA2 的确切细胞内功能仍未确定，并且比 ADA1 的定义更少。 ADA2 具有独特的特征，例如低腺苷亲和力、肝素结合能力和推定的溶酶体进入。在这里，我们确认 ADA2 是一种溶酶体蛋白，可结合 Toll 样受体 9 (TLR9​​) 激动剂，特别是 CpG 寡脱氧核苷酸 (CpG ODN)。我们发现，干扰素-α (IFN-α) 是响应 CpG ODN 和天然 DNA 激活 TLR9 而分泌的，并且当浆细胞样树突状细胞 (pDC) 中 ADA2 表达下调时，干扰素-α (IFN-α) 显着增加。此外，在用 CpG ODN 激活后，用 RNA 预处理 pDC 进一步刺激 pDC 分泌 IFN-α。我们的研究结果表明，ADA2 调节激活的 pDC 中 TLR9 对 DNA 的反应。总之，降低 ADA2 表达或用特定寡核苷酸阻断它可以增强 pDC 的 IFN-α 分泌，改善针对细胞内感染和癌症的免疫反应。© 2024。高等教育出版社。

Human cells contain two types of adenosine deaminases (ADA) each with unique properties: ADA1, which is present in all cells where it modulates intracellular functions and extracellular signaling, and ADA2, which is secreted by immune cells. The exact intracellular functions of ADA2 remain undetermined and less defined than those of ADA1. ADA2 has distinct characteristics, such as low adenosine affinity, heparin-binding ability, and putative lysosomal entry. Here, we confirm that ADA2 is a lysosomal protein that binds toll-like receptor 9 (TLR9) agonists, specifically CpG oligodeoxynucleotides (CpG ODNs). We show that interferon-alpha (IFN-α) is secreted in response to TLR9 activation by CpG ODNs and natural DNA and markedly increases when ADA2 expression is downregulated in plasmacytoid dendritic cells (pDCs). Additionally, the pretreatment of pDCs with RNA further stimulates IFN-α secretion by pDCs after activation with CpG ODNs. Our findings indicate that ADA2 regulates TLR9 responses to DNA in activated pDCs. In conclusion, decreasing ADA2 expression or blocking it with specific oligonucleotides can enhance IFN-α secretion from pDCs, improving immune responses against intracellular infections and cancer.© 2024. Higher Education Press.