ArticleNature2010
TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
208 citing papers in PubMed, 365 citations in OpenAlex.
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects.Arthritis research & therapy · 2019Trial
- Red blood cell distribution width-to-platelet ratio as a disease activity-associated factor in systemic lupus erythematosus.Medicine · 2018Trial
- Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.Clinical rheumatology · 2016Trial
- Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis.PloS one · 2014Trial
- Drugging endosomal flux.Nature chemical biology · 2026Article
- Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation.Nature chemical biology · 2026Article
- The use of glucocorticoids in immunoglobulin-resistant Kawasaki disease.Scientific reports · 2026Article
- Cationic microparticles inhibit local sterile inflammation in tissue injuries.Regenerative biomaterials · 2026Article
- Plasmacytoid dendritic cells in systemic and cutaneous lupus erythematosus: an evolving understanding.Frontiers in immunology · 2026Review
- An Overview of the Pathogenesis of Cutaneous Lupus Erythematosus.Journal of clinical medicine · 2025Review
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Knowledge mapping of plasmacytoid dendritic cells in systemic lupus erythematosus: a bibliometric analysis (2004-2023).Clinical rheumatology · 2025Article
- Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Afimetoran, a Toll-Like Receptor 7 and 8 Inhibitor, in Patients With Cutaneous Lupus Erythematosus: A Phase 1b Randomized, Double-Blind, Placebo-Controlled Study.ACR open rheumatology · 2025Article
- Defining immune reset: achieving sustained remission in autoimmune diseases.Nature reviews. Immunology · 2025Review
- Review
- Elevated serum interferon-α2 associates with activity and flare risk in juvenile-onset systemic lupus erythematosus.Rheumatology (Oxford, England) · 2025Article
- SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses.Nature communications · 2025Article
- Genomic analysis of progenitors in viral infection implicates glucocorticoids as suppressors of plasmacytoid dendritic cell generation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.The Journal of experimental medicine · 2025Article
- New Insights on Childhood Lupus Nephritis.International journal of nephrology and renovascular disease · 2025Review
148 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Glucocorticoids are widely used to treat patients with autoimmune diseases such as systemic lupus erythematosus (SLE). However, regimens used to treat many such conditions cannot maintain disease control in the majority of SLE patients and more aggressive approaches such as high-dose methylprednisolone pulse therapy are used to provide transient reductions in disease activity. The primary anti-inflammatory mechanism of glucocorticoids is thought to be NF-kappaB inhibition. Recognition of self nucleic acids by toll-like receptors TLR7 and TLR9 on B cells and plasmacytoid dendritic cells (PDCs) is an important step in the pathogenesis of SLE, promoting anti-nuclear antibodies and the production of type I interferon (IFN), both correlated with the severity of disease. Following their activation by self-nucleic acid-associated immune complexes, PDCs migrate to the tissues. We demonstrate, in vitro and in vivo, that stimulation of PDCs through TLR7 and 9 can account for the reduced activity of glucocorticoids to inhibit the IFN pathway in SLE patients and in two lupus-prone mouse strains. The triggering of PDCs through TLR7 and 9 by nucleic acid-containing immune complexes or by synthetic ligands activates the NF-kappaB pathway essential for PDC survival. Glucocorticoids do not affect NF-kappaB activation in PDCs, preventing glucocorticoid induction of PDC death and the consequent reduction of systemic IFN-alpha levels. These findings unveil a new role for self nucleic acid recognition by TLRs and indicate that inhibitors of TLR7 and 9 signalling could prove to be effective corticosteroid-sparing drugs.
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What OpenQuestion holds
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.