ArticleFrontiers in immunology2015
Female Bias in Systemic Lupus Erythematosus is Associated with the Differential Expression of X-Linked Toll-Like Receptor 8.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024Review
- The conneXion between sex and immune responses.Nature reviews. Immunology · 2024Review
- XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner.Biology of sex differences · 2024Article
- Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?Frontiers in immunology · 2024Review
- XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner.Research square · 2023Article
- The X in seX-biased immunity and autoimmune rheumatic disease.The Journal of experimental medicine · 2022Review
- Crosstalk between high-density lipoproteins and endothelial cells in health and disease: Insights into sex-dependent modulation.Frontiers in cardiovascular medicine · 2022Review
- MicroRNA-21 regulate the cell apoptosis and cell proliferation of polycystic ovary syndrome (PCOS) granulosa cells through target toll like receptor TLR8.Bioengineered · 2021Article
- X-factors in human disease: impact of gene content and dosage regulation.Human molecular genetics · 2021Review
- Variety of endosomal TLRs and Interferons (IFN-α, IFN-β, IFN-γ) expression profiles in patients with SLE, SSc and MCTD.Clinical and experimental immunology · 2021Article
- Leveraging Heterogeneity in Systemic Lupus Erythematosus for New Therapies.Trends in molecular medicine · 2021Review
- Time to get ill: the intersection of viral infections, sex, and the X chromosome.Current opinion in physiology · 2021Review
- Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.Frontiers in immunology · 2021Article
- When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity.Journal of leukocyte biology · 2019Review
- Sex, Symptom Severity, and Quality of Life in Rheumatology.Clinical reviews in allergy & immunology · 2019Review
- Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation.Seminars in immunopathology · 2019Review
- Sex bias in autoimmunity.Current opinion in rheumatology · 2019Review
- Review
- Effects of Major Epigenetic Factors on Systemic Lupus ErythematosusIranian biomedical journal · 2018Review
- New Advances in Human X chromosome status from a Developmental and Stem Cell Biology.Tissue engineering and regenerative medicine · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of anti-nuclear antibodies. SLE is one of many autoimmune disorders that have a strong gender bias, with 70-90% of SLE patients being female. Several explanations have been postulated to account for the severity of autoimmune diseases in females, including hormonal, microbiota, and gene dosage differences. X-linked toll-like receptors (TLRs) have recently been implicated in disease progression in females. Our previous studies using the 564Igi mouse model of SLE on a Tlr7 and Tlr9 double knockout background showed that the presence of Tlr8 on both X chromosomes was required for the production of IgG autoantibodies, Ifn-I expression and granulopoiesis in females. Here, we show the results of our investigation into the role of Tlr8 expression in SLE pathogenesis in 564Igi females. Female mice have an increase in serum pathogenic anti-RNA IgG2a and IgG2b autoantibodies. 564Igi mice have also been shown to have an increase in neutrophils in vivo, which are major contributors to Ifn-α expression. Here, we show that neutrophils from C57BL/6 mice express Ifn-α in response to 564 immune complexes and TLR8 activation. Bone marrow-derived macrophages from 564Igi females have a significant increase in Tlr8 expression compared to male-derived cells, and RNA fluorescence in situ hybridization data suggest that Tlr8 may escape X-inactivation in female-derived macrophages. These results propose a model by which females may be more susceptible to SLE pathogenesis due to inefficient inactivation of Tlr8.
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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 OpenQuestion graph.