ArticleThe Journal of experimental medicine2025
Mechanosensing regulates pDC activation in the skin through NRF2 activation.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- The skeletal muscle slow myosin heavy chain regulates mammalian metabolic homeostasis through the NRF2 pathway.Science advances · 2026Article
- Reactive oxygen species and metabolic checkpoints shape plasmacytoid dendritic cell fate in infection and autoimmunity.Redox biology · 2026Review
- CAR-T cells in systemic sclerosis.Clinical rheumatology · 2026Review
- Spatiotemporal Regulation of Ligand Trafficking and TLR9 Activation by PIEZO1 in Human Plasmacytoid Dendritic Cells.Research (Washington, D.C.) · 2026Article
- PIEZO1 in Immune Cells: From Force to Function.Results and problems in cell differentiation · 2026Review
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- PFKFB2-Driven Glycolysis Promotes Dendritic Cell Maturation and Exacerbates Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation.Cell communication and signaling : CCS · 2025Article
- Glutathione-ROS pathway activation by probiotic B240 augments macrophage response to influenza.Frontiers in cellular and infection microbiology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Plasmacytoid DCs (pDCs) infiltrate the skin, chronically produce type I interferon (IFN-I), and promote skin lesions and fibrosis in autoimmune patients. However, what controls their activation in the skin is unknown. Here, we report that increased stiffness inhibits the production of IFN-I by pDCs. Mechanistically, mechanosensing activates stress pathways including NRF2, which induces the pentose phosphate pathway and reduces pyruvate levels, a product necessary for pDC responses. Modulating NRF2 activity in vivo controlled the pDC response, leading to resolution or chronic induction of IFN-I in the skin. In systemic sclerosis (SSc) patients, although NRF2 was induced in skin-infiltrating pDCs, as compared with blood pDCs, the IFN response was maintained. We observed that CXCL4, a profibrotic chemokine elevated in fibrotic skin, was able to overcome stiffness-mediated IFN-I inhibition, allowing chronic IFN-I responses by pDCs in the skin. Hence, these data identify a novel regulatory mechanism exerted by the skin microenvironment and identify points of dysregulation of this mechanism in patients with skin inflammation and fibrosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.