2025/08/12 by Rebeca Arroyo Hornero, Raul A. Maqueda‐Alfaro, Miguel A. Solís‐Barbosa +5 · 1 voice · 1 citation
Immunology and Microbiology · #Immune Cell Function and Interaction #Immunotherapy and Immune Responses #T-cell and B-cell Immunology
paper · doi:10.1038/s41590-025-02234-3
openalex publication_date 2025/08/12 · openalex created_date 2025/08/14 · openalex updated_date 2026/08/01
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.