ArticleThe Journal of clinical investigation2019
The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.
- Higher disease reactivation risk in women after fingolimod withdrawal.Acta neuropathologica communications · 2026Pooled it
- Sex- and age-specific associations ofAnnals of medicine · 2026Article
- Nuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by regulating expression of AP-1 transcription factors and their target genes.Nucleic acids research · 2026Article
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Gonadal Sex and Sex-Chromosome Complement Interact to Affect Ethanol Consumption in Adolescent Four Core Genotypes Mice.Brain sciences · 2026Article
- Highlight on Dr. Rhonda Voskuhl: a pioneer in the exploration of sex differences in the immune response.Biology of sex differences · 2026Article
- Why Is MS a More Frequent Complication of EBV Infection in Females?Immunological reviews · 2026Review
- Sex differences in immune responses to viruses, bacteria and vaccines.Nature immunology · 2026Review
- Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sex as a Biological Variable in Tuberculosis Pathogenesis.Immunological reviews · 2026Review
- Sex Differences in the Impact of Obesity on Immunity.Immunological reviews · 2026Review
- Sry-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more.Biology of sex differences · 2026Article
- Sex and gender-related differences in neurological diseases: current challenges and recommendations for clinical practice.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Sex differences in innate immune cell responses: Impact on cancer immunity and response to therapy.Frontiers in immunology · 2026Review
- Deletion of the X-chromosomal geneScience translational medicine · 2025Article
- Multicondition and multimodal temporal profile inference during mouse embryonic development.Genome research · 2025Article
- Understanding Sex Differences in Autoimmune Diseases: Immunologic Mechanisms.International journal of molecular sciences · 2025Review
- Review
- The Inactive X Chromosome: A Genetic Driver of Female-Biased Rheumatic Autoimmune Disorders?European journal of immunology · 2025Review
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Multiple sclerosis (MS) is a putative T cell-mediated autoimmune disease. As with many autoimmune diseases, females are more susceptible than males. Sexual dimorphisms may be due to differences in sex hormones, sex chromosomes, or both. Regarding sex chromosome genes, a small percentage of X chromosome genes escape X inactivation and have higher expression in females (XX) compared with males (XY). Here, high-throughput gene expression analysis in CD4+ T cells showed that the top sexually dimorphic gene was Kdm6a, a histone demethylase on the X chromosome. There was higher expression of Kdm6a in females compared with males in humans and mice, and the four core genotypes (FCG) mouse model showed higher expression in XX compared with XY. Deletion of Kdm6a in CD4+ T cells ameliorated clinical disease and reduced neuropathology in the classic CD4+ T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis (EAE). Global transcriptome analysis in CD4+ T cells from EAE mice with a specific deletion of Kdm6a showed upregulation of Th2 and Th1 activation pathways and downregulation of neuroinflammation signaling pathways. Together, these data demonstrate that the X escapee Kdm6a regulates multiple immune response genes, providing a mechanism for sex differences in autoimmune disease susceptibility.
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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.