ArticleArthritis research & therapy2016
A functional variant of TLR10 modifies the activity of NFkB and may help predict a worse prognosis in patients with rheumatoid arthritis.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 44 citations in OpenAlex.
- Trial
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- Network pharmacology and experimental verification in vivo reveal the mechanism of Zhushao Granules against ulcerative colitis.Biological procedures online · 2025Article
- An Overview of Therapeutic Targeting of Nrf2 Signaling Pathway in Rheumatoid Arthritis.ACS omega · 2024Review
- Structural modelling and dynamics of full-length of TLR10 sheds light on possible modes of dimerization, ligand binding and mechanism of action.Current research in structural biology · 2023Article
- Differential Gene Expression Induced by Different TLR Agonists in A549 Lung Epithelial Cells Is Modulated by CRISPR Activation of TLR10.Biomolecules · 2022Article
- Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search.Rheumatology (Oxford, England) · 2022Review
- Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.International journal of molecular sciences · 2022Review
- Hepatitis C Virus Infection and Intrinsic Disorder in the Signaling Pathways Induced by Toll-Like Receptors.Biology · 2022Review
- Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?Biomolecules · 2021Review
- Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology.ImmunoTargets and therapy · 2021Review
- Increased Ratio of CD14Frontiers in immunology · 2021Article
- Selective sweep analysis reveals extensive parallel selection traits between large white and Duroc pigs.Evolutionary applications · 2020Article
- TLR10 and Its Unique Anti-Inflammatory Properties and Potential Use as a Target in Therapeutics.Immune network · 2020Review
- IL‑1β increases the expression of inflammatory factors in synovial fluid‑derived fibroblast‑like synoviocytes via activation of the NF‑κB‑mediated ERK‑STAT1 signaling pathway.Molecular medicine reports · 2019Article
- KDR (VEGFR2) Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis.Biomolecules · 2019Article
- IL-6: a cytokine at the crossroads of autoimmunity.Current opinion in immunology · 2018Review
- TLR10 and NFKBIA contributed to the risk of hip osteoarthritis: systematic evaluation based on Han Chinese population.Scientific reports · 2018Article
- Increased Expression of TLR10 in B Cell Subsets Correlates with Disease Activity in Rheumatoid Arthritis.Mediators of inflammation · 2018Article
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11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundToll-like receptor (TLR) family members are key players in inflammation. TLR10 has been poorly studied in chronic inflammatory disorders, and its clinical relevance in rheumatoid arthritis (RA) is as yet unknown. We aimed at identifying TLR10 variants within all coding regions of the gene in patients with RA as well as studying their functional and clinical significance.
methodsTLR10 gene variants were studied by performing sequencing of 66 patients with RA and 30 control subjects. A selected variant, I473T, was then analyzed in 1654 patients and 1702 healthy control subjects. The capacity of this TLR10 variant to modify the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) was determined by using a luciferase reporter assay and analyzing the expression of NFkB target genes by quantitative polymerase chain reaction. Differences between groups were analyzed by using the Mann-Whitney U test and the unpaired two-tailed Student's t test.
resultsWe detected ten missense variants in the TLR10 gene and focused on the I473T substitution based on allele frequencies and the predicted functional impact. I473T variant is not associated with susceptibility to RA, but it significantly correlates with erosive disease in patients seropositive for antibodies to citrullinated protein antigens (p = 0.017 in the total cohort and p = 0.0049 in female patients) and with a lower response to infliximab treatment as measured by the change in Disease Activity Score in 28 joints (p = 0.012) and by the European League Against Rheumatism criteria (p = 0.049). Functional studies showed that TLR10 reduced activation of the NFkB inflammatory pathway in hematopoietic cells, whereas the I473T variant lacked this inhibitory capacity. Consistently, after exposure to infliximab, cells expressing the I437T variant showed higher NFkB activity than cells carrying wild-type TLR10.
conclusionsA TLR10 allelic variant, I473T, has impaired NFkB inhibitory activity and is highly associated with disease severity and low response to infliximab in patients with RA.
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