ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in rheumatoid arthritis and experimental arthritis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses 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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Pooled it
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- TLR5 Signaling Causes Dendritic Cell Dysfunction and Orchestrates Failure of Immune Checkpoint Therapy against Ovarian Cancer.Cancer immunology research · 2025Article
- Review
- HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- Inhibition of IRAK4 dysregulates SARS-CoV-2 spike protein-induced macrophage inflammatory and glycolytic reprogramming.Cellular and molecular life sciences : CMLS · 2022Article
- The effects and significance of gut microbiota and its metabolites on the regulation of osteoarthritis: Close coordination of gut-bone axis.Frontiers in nutrition · 2022Review
- Metabolic regulation of RA macrophages is distinct from RA fibroblasts and blockade of glycolysis alleviates inflammatory phenotype in both cell types.Cellular and molecular life sciences : CMLS · 2021Article
- Upregulating miR-27a-3p inhibits cell proliferation and inflammation of rheumatoid arthritis synovial fibroblasts through targeting toll-like receptor 5.Experimental and therapeutic medicine · 2021Article
- IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion.Cellular & molecular immunology · 2021Article
- Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS-CoV-2 Spike protein.European journal of immunology · 2021Article
- Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?Biomolecules · 2021Review
- Bone Homeostasis and Gut Microbial-Dependent Signaling Pathways.Journal of microbiology and biotechnology · 2021Review
- CCL25 and CCR9 is a unique pathway that potentiates pannus formation by remodeling RA macrophages into mature osteoclasts.European journal of immunology · 2021Article
- Transcriptome-wide association study identifies susceptibility genes for rheumatoid arthritis.Arthritis research & therapy · 2021Article
- Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension.Scientific reports · 2021Article
- Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology.ImmunoTargets and therapy · 2021Review
- TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status.Rheumatology (Oxford, England) · 2020Article
- LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Our aim was to examine the impact of TLR5 ligation in rheumatoid arthritis (RA) and experimental arthritis pathology. Studies were conducted to investigate the role of TLR5 ligation on RA and mouse myeloid cell chemotaxis or osteoclast formation, and in addition, to uncover the significance of TNF-α function in TLR5-mediated pathogenesis. Next, the in vivo mechanism of action was determined in collagen-induced arthritis (CIA) and local joint TLR5 ligation models. Last, to evaluate the importance of TLR5 function in RA, we used anti-TLR5 Ab therapy in CIA mice. We show that TLR5 agonist, flagellin, can promote monocyte infiltration and osteoclast maturation directly through myeloid TLR5 ligation and indirectly via TNF-α production from RA and mouse cells. These two identified TLR5 functions are potentiated by TNF-α, because inhibition of both pathways can more strongly impair RA synovial fluid-driven monocyte migration and osteoclast differentiation compared with each factor alone. In preclinical studies, flagellin postonset treatment in CIA and local TLR5 ligation in vivo provoke homing and osteoclastic development of myeloid cells, which are associated with the TNF-α cascade. Conversely, CIA joint inflammation and bone erosion are alleviated when TLR5 function is blocked. We found that TLR5 and TNF-α pathways are interconnected, because TNF-α is produced by TLR5 ligation in RA myeloid cells, and anti-TNF-α therapy can markedly suppress TLR5 expression in RA monocytes. Our novel findings demonstrate that a direct and an indirect mechanism are involved in TLR5-driven RA inflammation and bone destruction.
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