ArticleJournal of autoimmunity2012
Environmental exposure, estrogen and two X chromosomes are required for disease development in an epigenetic model of lupus.
Article in Journal of autoimmunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Pooled it
- Prevalence and correlates of antinuclear antibodies in a Japanese community sample: a cross-sectional study.Current therapeutic research, clinical and experimental · 2026Article
- Fermentation time Determines Anti-inflammatory and Osteoprotective Activity of Green Tea Kombucha in a Rat Model of Experimental Periodontitis.Probiotics and antimicrobial proteins · 2026Article
- Article
- Effects of methotrexate on Wnt/β-catenin signaling and glial activation in temporomandibular joint arthritis in rats.European journal of oral sciences · 2025Article
- Environmental Xenobiotics and Epigenetic Modifications: Implications for Human Health and Disease.Journal of xenobiotics · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Temporomandibular joint arthritis increases canonical Wnt pathway expression in the articular cartilage and trigeminal ganglion in rats.Bone reports · 2023Article
- Differential impact of environmental factors on systemic and localized autoimmunity.Frontiers in immunology · 2023Review
- How does age determine the development of human immune-mediated arthritis?Nature reviews. Rheumatology · 2022Review
- Assessing the suitability of long non-coding RNAs as therapeutic targets and biomarkers in SARS-CoV-2 infection.Frontiers in molecular biosciences · 2022Review
- miR-31-5p Regulates Type I Interferon by Targeting SLC15A4 in Plasmacytoid Dendritic Cells of Systemic Lupus Erythematosus.Journal of inflammation research · 2022Article
- A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity.Frontiers in immunology · 2022Article
- Insights Into the Role of DNA Methylation in Immune Cell Development and Autoimmune Disease.Frontiers in cell and developmental biology · 2021Review
- CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease.Journal of clinical medicine · 2020Review
- Regulation of the germinal center response by nuclear receptors and implications for autoimmune diseases.The FEBS journal · 2020Review
- The Long Non-coding RNAs: Paramount Regulators of the NLRP3 Inflammasome.Frontiers in immunology · 2020Review
- Article
- The interaction between environmental triggers and epigenetics in autoimmunity.Clinical immunology (Orlando, Fla.) · 2018Review
- Effect of Lang-Chuang-Ding Decoction () on DNA Methylation of CD70 Gene Promoter in Peripheral Blood Mononuclear Cells of Female Patients with Systemic Lupus Erythematosus.Chinese journal of integrative medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for a dominant-negative MEK (dnMEK) that was previously shown to be inducibly and selectively expressed in T cells. In this model, induction of the dnMEK by doxycycline treatment suppresses T cell ERK signaling, decreasing DNA-methyltransferase expression and resulting in DNA demethylation, overexpression of immune genes Itgal (CD11a) and Tnfsf7 (CD70), and anti-dsDNA antibody. To examine the role of gender and estrogen in this model, male and female transgenic mice were neutered and implanted with time-release pellets delivering placebo or estrogen. Doxycycline induced IgG anti-dsDNA antibodies in intact and neutered, placebo-treated control female but not male transgenic mice. Glomerular IgG deposits were also found in the kidneys of female but not male transgenic mice, and not in the absence of doxycycline. Estrogen enhanced anti-dsDNA IgG antibodies only in transgenic, ERK-impaired female mice. Decreased ERK activation also resulted in overexpression and demethylation of the X-linked methylation-sensitive gene CD40lg in female but not male mice, consistent with demethylation of the second X chromosome in the females. The results show that both estrogen and female gender contribute to the female predisposition in lupus susceptibility through hormonal and epigenetic X-chromosome effects and through suppression of ERK signaling by environmental agents.
Indexed as
Identifiers
What OpenQuestion holds
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.