ArticleArthritis research & therapy2016
Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists.
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 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
- Differential regulation of monocyte exhaustion by distinct TLR agonists and underlying mechanisms.Cell communication and signaling : CCS · 2026Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- TLR9: A Double-Dealing Toll-Like Receptor.ImmunoTargets and therapy · 2025Review
- Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review.American journal of medicine open · 2024Article
- Cytoplasmic DNA and AIM2 inflammasome in RA: where they come from and where they go?Frontiers in immunology · 2024Review
- Effect of the immune cells and plasma metabolites on rheumatoid arthritis: a mediated mendelian randomization study.Frontiers in endocrinology · 2024Article
- Innate immune memory in inflammatory arthritis.Nature reviews. Rheumatology · 2023Review
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes.Frontiers in endocrinology · 2023Article
- CD169+ Monocyte and Regulatory T Cell Subsets Are Associated with Disease Activity in Rheumatoid Arthritis.Journal of personalized medicine · 2022Article
- Antiviral Innate Immune Responses in Autoimmunity: Receptors, Pathways, and Therapeutic Targeting.Biomedicines · 2022Review
- Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells.International journal of molecular sciences · 2022Article
- Immunometabolic adaptation and immune plasticity in pregnancy and the bi-directional effects of obesity.Clinical and experimental immunology · 2022Article
- The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis.Frontiers in immunology · 2022Review
- Association of TLR 9 gene polymorphisms with remission in patients with rheumatoid arthritis receiving TNF-α inhibitors and development of machine learning models.Scientific reports · 2021Article
- Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis.Cells · 2021Review
- Toll-like Receptor 2 in Autoimmune Inflammation.Immune network · 2021Review
- Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?Arthritis research & therapy · 2021Article
- Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications.Frontiers in immunology · 2021Review
- Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology.ImmunoTargets and therapy · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSynovial infiltration of monocytes is commonly associated with inflammation in rheumatoid arthritis (RA). Toll-like receptors (TLRs) are innate sensors that recognize cell debris and microbial components in host, a process contributing to maintain chronic inflammation in RA. We assessed the expression levels of TLR2 and TLR9 in monocyte subsets of active RA patients and characterized their cytokine profiles in response to synthetic and viral TLR2 and TLR9 agonists, including Epstein-Barr virus (EBV) which is suspected to contribute to RA symptoms.
methodsPrevalence of monocyte subsets CD14(++) CD16(-), CD14(+) CD16(+) and CD14(low) CD16(++) was evaluated in blood and synovial fluids of active RA patients and levels of TLR2 and TLR9 in monocyte subsets were measured by flow cytometry. Enriched monocytes derived from RA patients and healthy donors were stimulated in vitro with synthetic TLR2 and TLR9 agonists and with EBV particles or viral DNA. Intracellular cytokine profiles were determined in respective monocyte subsets. Finally, the presence of EBV genome was evaluated by real-time PCR in blood and synovial monocytes of RA patients.
resultsNumbers of CD14(+) CD16(+) and CD14(low) CD16(++) were found to increase in blood of RA patients compared to healthy controls, while all three subsets were detected in synovial fluids. TLR2 is abundantly expressed on blood and synovial CD14(++) CD16(-) and CD14(+) CD16(+) monocytes from RA patients. Levels of TLR9 were increased on all three subsets of blood monocytes but markedly enhanced in monocytes isolated from synovial fluids. Compared to healthy controls, CD14(++) CD16(-) monocytes of RA patients displayed an enlarged capacity to produce proinflammatory cytokines after stimulation with synthetic TLR2 and TLR9 agonists while both CD14(++) CD16(-) and CD14(+) CD16(+) monocytes showed increased response to EBV stimulation. The presence of EBV genome was also detected in monocytes and neutrophils of a significant proportion of patients.
conclusionPatients with active RA show an increased expression of TLR2 and TLR9 on monocyte subsets and display higher production of inflammatory cytokines in response to TLR agonists. The presence of EBV genome in monocytes and neutrophils reinforces the suspected role of the virus in the exacerbation of RA symptoms.
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