加州大学圣地亚哥分校医学院Juliana Idoyaga小组在研究中取得进展。他们探明了TNF和I型干扰素串扰控制浆细胞样树突状细胞的命运和功能。相关论文发表在2025年8月12日出版的《自然—免疫学》杂志上。

在这里，研究团队通过单细胞组学和功能实验来证明，激活的人类pDCs可以失去其作为IFN-I分泌细胞的身份，并获得cDC的转录、表观遗传和功能特征。这种pDC命运转换过程由肿瘤坏死因子促进，但被IFN-I阻断。重要的是，它发生在人体皮肤炎症性疾病和损伤期间，也发生在老年人的生理上。这项工作确定了pDC到cDC的重编程轨迹，并揭示了利用它进行治疗的机制框架。

据介绍，浆细胞样树突状细胞（pDCs）是I型干扰素（IFN-I）的主要产生者，IFN-I是一种重要的抗病毒细胞因子，这些细胞的活性必须受到严格控制，以防止有害的炎症和自身免疫。有证据表明，从分泌IFN-I的pDC到缺乏分泌IFN-I能力的专业抗原呈递常规树突状细胞（cDC）的命运转换过程是一种调控机制。然而，这种分化过程是有争议的，因为跟踪单个细胞的命运随时间的限制。

附：英文原文

Title: TNF and type I interferon crosstalk controls the fate and function of plasmacytoid dendritic cells

Author: Arroyo Hornero, Rebeca, Maqueda-Alfaro, Raul A., Sols-Barbosa, Miguel A., Leylek, Rebecca A., Medina Chavez, Olin, Martinez, Olivia M., Gottfried-Blackmore, Andres, Idoyaga, Juliana

Issue&Volume: 2025-08-12

Abstract: Plasmacytoid dendritic cells (pDCs) are major producers of type I interferon (IFN-I), an important antiviral cytokine, and activity of these cells must be tightly controlled to prevent harmful inflammation and autoimmunity. Evidence exists that one regulatory mechanism is a fate-switching process from an IFN-I-secreting pDC to a professional antigen-presenting conventional dendritic cell (cDC) that lacks IFN-I-secreting capacity. However, this differentiation process is controversial owing to limitations in tracking the fate of individual cells over time. Here we use single-cell omics and functional experiments to show that activated human pDCs can lose their identity as IFN-I-secreting cells and acquire the transcriptional, epigenetic and functional features of cDCs. This pDC fate-switching process is promoted by tumor necrosis factor but blocked by IFN-I. Importantly, it occurs in vivo during human skin inflammatory diseases and injury, and physiologically in elderly people. This work identifies the pDC-to-cDC reprogramming trajectory and unveils a mechanistic framework for harnessing it therapeutically.

DOI: 10.1038/s41590-025-02234-3

Source: https://www.nature.com/articles/s41590-025-02234-3