ArticleThe Journal of experimental medicine2013
RNA recognition by human TLR8 can lead to autoimmune inflammation.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
119 citing papers in PubMed, 199 citations in OpenAlex.
- First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MHV370, a Dual Inhibitor of Toll-Like Receptors 7 and 8, in Healthy Adults.European journal of drug metabolism and pharmacokinetics · 2023Trial
- Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans.The Journal of allergy and clinical immunology · 2019Trial
- TLR8 gain-of-function syndrome.Journal of human immunity · 2026Article
- ANGPTL2 inhibits macrophage pyroptosis and alleviates rheumatoid arthritis progression by regulating mitophagy via IGFBP5.Cell death & disease · 2026Article
- Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome.JCI insight · 2026Article
- Investigating Dysregulated X Chromosome Inactivation in Human B Cells and Plasmacytoid Dendritic Cells by RNA FISH.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Autoimmune fibroinflammation in IgG4-related ophthalmic disease: TLR8-dependent signaling pathways and fibrotic remodeling revealed by proteomic profiling.Frontiers in immunology · 2026Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- The Inactive X Chromosome: A Genetic Driver of Female-Biased Rheumatic Autoimmune Disorders?European journal of immunology · 2025Review
- Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.The Journal of experimental medicine · 2025Article
- Piggybacking on nature: exploring the multifaceted world of porcine β-defensins.Veterinary research · 2025Review
- Loss of STIM1 and STIM2 in Salivary Glands Disrupts ANO1 Function but Does Not Induce Sjogren's Disease.Function (Oxford, England) · 2025Article
- Mechanisms and effects of activation of innate immunity by mitochondrial nucleic acids.International immunology · 2025Review
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Toll-Like Receptor 8 is Expressed in Monocytes in Contrast to Plasmacytoid Dendritic Cells and Mediates Aberrant Interleukin-10 Responses in Patients With Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- TBK1 and Caspase-8 suppress necroptosis but activate NLRP3 inflammasome activation during CXCL4 and TLR8 costimulation.Cell death discovery · 2024Article
- Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024Review
- The path ahead for understanding Toll-like receptor-driven systemic autoimmunity.Current opinion in immunology · 2024Review
59 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies on the role of the RNA receptor TLR8 in inflammation have been limited by its different function in human versus rodents. We have generated multiple lines of transgenic mice expressing different levels of human TLR8. The high copy number chimeras were unable to pass germline; developed severe inflammation targeting the pancreas, salivary glands, and joints; and the severity of the specific phenotypes closely correlated with the huTLR8 expression levels. Mice with relatively low expression levels survived and bred successfully but had increased susceptibility to collagen-induced arthritis, and the levels of huTLR8 correlated with proinflammatory cytokines in the joints of the animals. At the cellular level, huTLR8 signaling exerted a DC-intrinsic effect leading to up-regulation of co-stimulatory molecules and subsequent T cell activation. A pathogenic role for TLR8 in human diseases was suggested by its increased expression in patients with systemic arthritis and the correlation of TLR8 expression with the elevation of IL-1β levels and disease status. We found that the consequence of self-recognition via TLR8 results in a constellation of diseases, strikingly distinct from those related to TLR7 signaling, and points to specific inflammatory diseases that may benefit from inhibition of TLR8 in humans.
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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.