Nature Immunology, Published online: 12 August 2025; doi:10.1038/s41590-025-02234-3

Plasmacytoid dendritic cells are type 1 interferon (IFN-I)-producing antiviral specialists that have been shown to be able to differentiate into conventional dendritic cells. Here the authors show how this differentiation is controlled by tumor necrosis factor driving type 2 conventional dendritic cell-like reprogramming and IFN-I blocking it, a process that occurs during inflammation, injury and aging.



Summary

A Nature Immunology article reveals new insights into plasmacytoid dendritic cell (pDC) differentiation. pDCs, known for their antiviral IFN-I production, can transform into conventional dendritic cells (cDCs). This study demonstrates that tumor necrosis factor (TNF) triggers a reprogramming process, pushing pDCs towards a type 2 cDC-like state. Conversely, IFN-I, the pDC’s primary product, actively inhibits this differentiation. This delicate balance, controlled by TNF and IFN-I, plays a crucial role during inflammation, injury, and aging, influencing the immune response. Understanding this mechanism may offer new therapeutic targets for modulating immunity in these contexts.

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