ArticlePloS one2013
Multiple sclerosis: modulation of toll-like receptor (TLR) expression by interferon-β includes upregulation of TLR7 in plasmacytoid dendritic cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Meta-Analysis of Differential Connectivity in Gene Co-Expression Networks in Multiple Sclerosis.International journal of molecular sciences · 2016Pooled it
- Up-Regulation of TLR7-Mediated IFN-α Production by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus.Frontiers in immunology · 2018Trial
- Microglia-Derived Extracellular Vesicles from Alzheimer's Disease Patients Carry miRNAs Driving a Neuroinflammatory Response.Molecular neurobiology · 2026Article
- Host-pathogen protein-nucleic acid interactions: A comprehensive review.Computational and structural biotechnology journal · 2022Review
- Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems.Frontiers in immunology · 2021Review
- Activation of Toll-like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients.Clinical and experimental immunology · 2019Article
- Engineering release kinetics with polyelectrolyte multilayers to modulate TLR signaling and promote immune tolerance.Biomaterials science · 2019Article
- Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren's Syndrome.International journal of molecular sciences · 2018Review
- Enhanced IFN-α production is associated with increased TLR7 retention in the lysosomes of palasmacytoid dendritic cells in systemic lupus erythematosus.Arthritis research & therapy · 2017Article
- Engineering self-assembled materials to study and direct immune function.Advanced drug delivery reviews · 2017Review
- Close Encounters of the First Kind: Innate Sensors and Multiple Sclerosis.Molecular neurobiology · 2017Review
- Article
- RNA sensing by conventional dendritic cells is central to the development of lupus nephritis.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Immunomodulatory activity of interferon-beta.Annals of clinical and translational neurology · 2014Review
- The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention.The EPMA journal · 2014Article
- The role of dendritic cells in tissue-specific autoimmunity.Journal of immunology research · 2014Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-β is an established treatment for patients with multiple sclerosis (MS) but its mechanisms of action are not well understood. Viral infections are a known trigger of MS relapses. Toll-like receptors (TLRs) are key components of the innate immune system, which sense conserved structures of viruses and other pathogens. Effects of interferon-β on mRNA levels of all known human TLRs (TLR1-10) and the TLR adaptor molecule MyD88 were analyzed in peripheral blood mononuclear cells (PBMCs) of healthy donors by quantitative real-time PCR and by transcriptome analysis in PBMCs of 25 interferon-β-treated patients with relapsing-remitting MS. Regulation of TLR protein expression by interferon-β was investigated by flow cytometry of leukocyte subsets of healthy subjects and of untreated, interferon-β-, or glatiramer acetate-treated patients with MS. Interferon-β specifically upregulated mRNA expression of TLR3, TLR7, and MyD88 and downregulated TLR9 mRNA in PBMCs of healthy donors as well as in PBMCs of patients with MS. Plasmacytoid dendritic cells (pDCs) were identified as the major cell type responding to interferon-β with increased expression of TLR7 and MyD88 protein. In line with this, expression of TLR7 protein was increased in pDCs of interferon-β-treated, but not untreated or glatiramer acetate-treated patients with MS. Interferon-β-induced upregulation of TLR7 in pDCs is of functional relevance since pre-treatment of PBMCs with interferon-β resulted in a strongly increased production of interferon-α upon stimulation with the TLR7 agonist loxoribine. Flow cytometry confirmed pDCs as the cellular source of interferon-α production induced by activation of TLR7. Thus, upregulation of TLR7 in pDCs and a consequently increased activation of pDCs by TLR7 ligands represents a novel immunoregulatory mechanism of interferon-β. We hypothesize that this mechanism could contribute to a reduction of virus-triggered relapses in patients with MS.
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