ArticleThe Journal of experimental medicine2025
Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.
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 16 papers.
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Who cites it
16 citing papers in PubMed.
- Sex-dependent mechanisms in rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.Journal of translational autoimmunity · 2026Review
- Reactive oxygen species and metabolic checkpoints shape plasmacytoid dendritic cell fate in infection and autoimmunity.Redox biology · 2026Review
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.Frontiers in immunology · 2026Review
- Long noncoding RNA regulation of immunity.Nature immunology · 2026Review
- Investigating Dysregulated X Chromosome Inactivation in Human B Cells and Plasmacytoid Dendritic Cells by RNA FISH.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Tonic type I interferon signaling optimizes the antiviral function of plasmacytoid dendritic cells.Nature immunology · 2025Article
- Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences.Clinical reviews in allergy & immunology · 2025Review
- The Inactive X Chromosome: A Genetic Driver of Female-Biased Rheumatic Autoimmune Disorders?European journal of immunology · 2025Review
- More X's, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity.Current opinion in immunology · 2025Review
- Mechanosensing regulates pDC activation in the skin through NRF2 activation.The Journal of experimental medicine · 2025Article
- Sex differences in systemic sclerosis: from pathogenesis to clinical manifestations and treatment.Therapeutic advances in musculoskeletal disease · 2025Review
- A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways.Frontiers in immunology · 2025Review
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
Systemic sclerosis (SSc) is an autoimmune disease that has a strong female predominance. Both the X-linked TLR7 and TLR8 can induce type I IFN (IFN-I) by plasmacytoid DCs (pDCs), which can promote fibrosis. We identified five subclusters of pDCs, including ISGhigh clusters that were over-represented in SSc patients. We observed that both TLR7 and TLR8 genes escape from X chromosome inactivation (XCI) at higher frequency in pDCs of SSc patients, which was associated with changes in TLR7 protein profile. Combined DNA/RNA FISH analysis revealed that the TLR7/8 locus is preferentially located outside of the inactive X (Xi) territory when TLR7 is expressed, suggesting that higher-order loop formation is linked to TLR7/8 expression from the Xi. Furthermore, the expression levels of XIST and the transcriptional repressor SPEN were reduced in SSc pDCs. Hence, our data revealed the heterogeneity of pDCs in SSc and suggested that altered XCI at the TLR7/8 locus may contribute to the chronic IFN-I activity of pDCs in female SSc patients.
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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.