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Reactive oxygen species and metabolic checkpoints shape plasmacytoid dendritic cell fate in infection and autoimmunity

Year: 2026

Type: article

Abstract: Plasmacytoid dendritic cells (pDCs) are innate immune sentinels uniquely specialised in the rapid and potent production of type I interferons (IFN-I) during viral infection. While this capacity is essential for antiviral defence, sustained pDC activation is a central feature of numerous autoimmune and inflammatory disorders. Although the molecular pathways governing nucleic acid sensing and IFN-I induction have been extensively characterised, the metabolic and redox mechanisms that support, and limit pDC function remain incompletely understood. Emerging studies reveal that pDC activity is tightly linked to a specialised redox-metabolic programme involving mitochondrial respiration, reactive oxygen species (ROS), and endolysosomal signalling networks. In this review, we integrate current evidence to propose that pDCs operate within a tightly regulated redox window that permits effective acute antiviral responses but renders them vulnerable to metabolic stress and dysregulation upon chronic stimulation. We examine how mitochondrial fitness, NAD + homeostasis, ROS dynamics, and endolysosomal redox control collectively influence pDC activation, resolution of inflammation, and pathogenic persistence. By reframing pDC biology through a redox-metabolic perspective, we highlight new conceptual insights into IFN-I-driven disease and identify potential therapeutic strategies to selectively modulate pathogenic pDC responses.

Source: Redox Biology

DOI: 10.1016/j.redox.2026.104185

Authors: Lena Rueschpler, Sebastian Schloer

Institutions: Leibniz Institute of Virology (LIV), University Medical Center Hamburg-Eppendorf

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,310