近日，美国纽约大学格罗斯曼医学院教授Boris Reizis及其团队的研究认为强I型干扰素信号优化浆细胞样树突状细胞的抗病毒功能。相关论文发表在2025年10月14日出版的《自然—免疫学》杂志上。

在这里，研究人员报告了幼稚小鼠的外周pDCs包括三个亚群（称为A， B和C），代表了进行性分化阶段。这种异质性是由cGAS/STING和TLR9 DNA传感途径部分引发的IFN-I信号传导所产生的。一个小的“IFN-I幼稚”子集（pDC-A）可能会产生其他子集；它在STING缺乏或IFN-I受体阻断后扩增，但被外源干扰素IFN-I消除。在RNA病毒主题的反应中，pDC-A表现出Bcl2依赖性生存和更好的IFN-I反应，但对病毒感染敏感。相反，大多数pDCs包含“IFN-I引物”亚群（pDC-B/C），表现出较低的IFN-I应答和较差的存活率，但不支持病毒复制。因此，补品IFN-I信号传导降低了pDCs的细胞因子产生能力和存活率，但增加了它们的病毒抗性，促进了最佳的抗病毒反应。

据悉，浆细胞样树突状细胞（pDCs）产生强大的抗病毒I型干扰素（IFN-I）反应，但只有一小部分pDCs产生高水平的IFN-I。

附：英文原文

Title: Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells

Author: Pucella, Joseph N., Maqueda-Alfaro, Raul A., Ni, Hai, Bandeira Sulczewski, Fernando, Eichinger, Anna, Esteva, Eduardo, Ra, Ai C., Das, Annesa, Perez, Oriana A., Feng, Jue, Stoeckius, Marlon, Smibert, Peter, Khodadadi-Jamayran, Alireza, Dolgalev, Igor, Ivanova, Ellie, Sota, Stela, Cadwell, Ken, Koralov, Sergei B., Zhong, Judy, Soni, Chetna, Stetson, Daniel B., Weisberg, Stuart P., Farber, Donna L., Idoyaga, Juliana, Reizis, Boris

Issue&Volume: 2025-10-14

Abstract: Plasmacytoid dendritic cells (pDCs) mount powerful antiviral type I interferon (IFN-I) responses, yet only a fraction of pDCs produces high levels of IFN-I. Here we report that peripheral pDCs in naive mice comprise three subsets (termed A, B and C) that represent progressive differentiation stages. This heterogeneity was generated by tonic IFN-I signaling elicited in part by the cGAS/STING and TLR9 DNA-sensing pathways. A small ‘IFN-I-naive’ subset (pDC-A) could give rise to other subsets; it was expanded in STING deficiency or after the IFN-I receptor blockade, but was abolished by exogenous IFN-I. In response to RNA viruses, pDC-A showed increased Bcl2-dependent survival and superior IFN-I responses, but was susceptible to virus infection. Conversely, the majority of pDCs comprised the ‘IFN-I-primed’ subsets (pDC-B/C) that showed lower IFN-I responses and poor survival, but did not support virus replication. Thus, tonic IFN-I signaling decreases the cytokine-producing capacity and survival of pDCs but increases their virus resistance, facilitating optimal antiviral responses.

DOI: 10.1038/s41590-025-02279-4

Source: https://www.nature.com/articles/s41590-025-02279-4