美国德克萨斯大学达拉斯西南医学中心免疫学系闫楠研究小组揭示了OAS通过2-5A的细胞间转移，在细胞间交叉激活RNase L，传播先天免疫。2025年2月25日出版的《免疫学》杂志发表了这项成果。

该团队发现2-5A通过连接蛋白（CX43/CX45）间隙连接在细胞间传递。2-5A也通过进口商和出口商转移，允许OAS远程激活RNase L并保护邻近细胞免受病毒感染。小组确定ABCC10为2-5A出口商。ABCC10的缺失对2-5A的产生没有影响，但减少了2-5A的输出和对邻近细胞的保护。

此外，OAS^hi肿瘤如MC38在体内自然产生2-5A，通过ABCC10分泌，激活宿主非肿瘤rnase l介导的抗肿瘤反应。因此，2-5A是一种介导感染与肿瘤细胞间短距离通讯的免疫递质。

据了解，2 '',5 '' -寡聚腺苷酸合成酶(OAS)-RNase L途径是经典的抗病毒先天免疫途径。在感知到dsRNA后，OAS产生2 '',5 '' -oligoadenylate （2-5A）作为激活RNase l的第二信使，2-5A是否可以被转运以扩大先天免疫信号的范围尚未确定。

附：英文原文

Title: OAS cross-activates RNase L intercellularly through cell-to-cell transfer of 2-5A to spread innate immunity

Author: Wanwan Huai, Kun Yang, Cong Xing, Kun Song, Heng Lyu, Noelle S. Williams, Jianjun Wu, Nan Yan

Issue&Volume: 2025-02-25

Abstract: The 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway is a classical antiviral innate immune pathway. Upon sensing dsRNA, OAS produces 2′,5′-oligoadenylate (2-5A) as a second messenger to activate RNase L. Whether 2-5A can be transported to extend the reach of innate immune signaling has not been established. Here, we showed that 2-5A was transferred from cell to cell through connexin (CX43/CX45) gap junctions. 2-5A was also transferred through importers and exporters, allowing OAS to remotely activate RNase L and protect neighboring cells from viral infection. We identified ABCC10 as a 2-5A exporter. Loss of ABCC10 had no effect on 2-5A production but reduced 2-5A export and protection of neighboring cells. Furthermore, OAS^hi tumors such as MC38 naturally produced 2-5A in vivo, which was secreted via ABCC10 to activate host—not tumor—RNase L-mediated antitumor response. Therefore, 2-5A is an immunotransmitter that mediates short-range communication between cells in infection and cancer.

DOI: 10.1016/j.immuni.2025.01.016

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00065-2