ArticlePLoS genetics2013
Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.Human molecular genetics · 2018Trial
- Regulatory T cells in axial spondyloarthritis.Communications biology · 2026Review
- Identifying genetic and cellular connections and distinctions among 15 autoimmune diseases using an in-silico approach.Communications medicine · 2026Article
- Autoimmunity-Associated SNP rs3024505 Disrupts STAT3 Binding in B Cells, Leading to IL10 Dysregulation.International journal of molecular sciences · 2024Article
- The Impact of the IL-10 Gene Polymorphism on mRNA Expression and IL-10 Serum Concentration in Polish Lupus Patients.International journal of molecular sciences · 2024Article
- B lymphocytes in treatment-naive paediatric patients with lupus are epigenetically distinct from healthy children.Lupus science & medicine · 2023Article
- Up-Regulated Interleukin-10 Induced by E2F Transcription Factor 2-MicroRNA-17-5p Circuitry in Extrafollicular Effector B Cells Contributes to Autoantibody Production in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.Nature communications · 2021Article
- Asymmetric Divergence in Transmitted SNPs of DNA Replication/Transcription and Their Impact on Gene Expression in PolyploidFrontiers in genetics · 2021Article
- Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals.Annals of the rheumatic diseases · 2019Article
- The Post-GWAS Era: How to Validate the Contribution of Gene Variants in Lupus.Current rheumatology reports · 2019Review
- Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus.Mediators of inflammation · 2019Article
- Dysregulated heme oxygenase-1Arthritis research & therapy · 2018Article
- Updates in Lupus Genetics.Current rheumatology reports · 2017Review
- Etv5 Regulates IL-10 Production in Th Cells.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production.Annals of the rheumatic diseases · 2016Article
- B cells gone rogue: the intersection of diffuse large B cell lymphoma and autoimmune disease.Expert review of hematology · 2016Review
- Therapeutic potential of regulatory cytokines that target B cells.International immunology · 2016Review
- Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.Nature genetics · 2015Article
Corrections and comments
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Authors and funding
46 authors at 19 institutions in 8 countries.
Funding
Abstract
Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10⁻⁸, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.
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