ArticleNeurology(R) neuroimmunology & neuroinflammation2022
Cell-Free DNA Derived From Neutrophils Triggers Type 1 Interferon Signature in Neuromyelitis Optica Spectrum Disorder.
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Article in Neurology(R) neuroimmunology & neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 41 citations in OpenAlex.
- The cGAS-STING Pathway: A Double-Edged Regulator of Neuroinflammation and Myelin Regeneration.Molecular neurobiology · 2026Review
- Neutrophil extracellular traps exacerbate blood-brain barrier disruption in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2026Article
- Nanocomposite LL37-gold nanoparticles with puerarin for periodontitis-linked atherosclerosis.Journal of nanobiotechnology · 2026Article
- Remnant cholesterol and lipid ratios predict the relapse of neuromyelitis optica spectrum disorder.Lipids in health and disease · 2026Article
- Type I Interferon Signaling Augments Autoimmunity in Neuromyelitis Optica Spectrum Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pilot Exploration of RGMa-BMP4 Signaling in Neutrophil Activation in NMOSD: Integrating Clinical and Molecular Insights.Molecular neurobiology · 2025Article
- Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering.Frontiers in immunology · 2025Article
- Cell-free DNA integrity and complement C4d as novel liquid biopsy biomarkers for paraneoplastic and non-paraneoplastic autoimmune encephalitis.Frontiers in immunology · 2025Article
- Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation.Cell host & microbe · 2024Article
- Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder.International journal of molecular sciences · 2024Article
- Neural-net-based cell deconvolution from DNA methylation reveals tumor microenvironment associated with cancer prognosis.NAR cancer · 2024Article
- Long-term Effects of IL-6 Receptor Blockade Therapy on Regulatory Lymphocytes and Neutrophils in Neuromyelitis Optica Spectrum Disorder.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.The Journal of clinical investigation · 2023Article
- Immune Repertoire Profiling Reveals Its Clinical Application Potential and Triggers for Neuromyelitis Optica Spectrum Disorders.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2023Article
- Autoimmune-mediated astrocytopathy.Inflammation and regeneration · 2023Review
- Who and how, DNA sensors in NETs-driven inflammation.Frontiers in immunology · 2023Review
- Systemic inflammation response index is a useful indicator in distinguishing MOGAD from AQP4-IgG-positive NMOSD.Frontiers in immunology · 2023Article
- Impaired response of blood neutrophils to cell-death stimulus differentiates AQP4-IgG-seropositive NMOSD from MOGAD.Journal of neuroinflammation · 2022Article
- Identifying different cognitive phenotypes and their relationship with disability in neuromyelitis optica spectrum disorder.Frontiers in neurology · 2022Article
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Authors and funding
15 authors at 1 institution in 1 country.
Hisashi MurataFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Makoto KinoshitaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan. mkinoshita@neurol.med.osaka-u.ac.jp.
Yoshiaki YasumizuFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.ORCID 0000-0002-9872-4909
Daisuke MotookaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Shohei BeppuFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Naoyuki ShiraishiFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Yasuko SugiyamaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Keigo KiharaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Satoru TadaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Toru KodaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Hachiro KonakaFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Hyota TakamatsuFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Atsushi KumanogohFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Tatsusada OkunoFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Hideki MochizukiFrom the Department of Neurology (Hisashi Murata, M.K., Y.Y., S.B., N.S., Y.S., K.K., S.T., T.K., T.O., Hideki Mochizuki), Graduate School of Medicine, Osaka University; Department of Experimental Immunology (Y.Y.), WPI Immunology Frontier Research Center, Osaka University; Integrated Frontier Research for Medical Science Division (Y.Y., D.M., A.K., Hideki Mochizuki), Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University; Genome Information Research Center (D.M.), Research Institute for Microbial Diseases, Osaka University; and Department of Respiratory Medicine and Clinical Immunology (H.K., H.T., A.K.), Graduate School of Medicine, Osaka University, Suita, Japan.
Murata (Japan) · JP
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesRecently accumulating evidence suggests the pivotal role of type 1 interferon (IFN-1) signature in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism of the initial trigger that augments IFN-1 pathway in the peripheral immune system of NMOSD has yet to be elucidated.
methodsClinical samples were obtained from 32 patients with aquaporin-4 antibody-positive NMOSD and 23 healthy subjects. IFN-1 induction in peripheral blood mononuclear cells (PBMCs) by serum-derived cell-free DNA (cfDNA) was assessed in combination with blockades of DNA sensors in vitro. CfDNA fraction was analyzed for DNA methylation profiles by bisulfite sequencing, elucidating the cellular origin of cfDNA. The induction of neutrophil extracellular trap related cell death (NETosis) was further analyzed in NMOSD and control groups, and the efficacy of pharmacologic intervention of NETosis was assessed.
resultsEnhanced IFN-1 induction by cfDNA derived from NMOSD was observed in PBMCs with cofactor of LL37 antimicrobial peptide. DNase treatment, cGAS inhibitor, and Toll-like receptor 9 antagonist efficiently inhibited IFN-1 production. DNA methylation pattern of cfDNA in patients with NMOSD demonstrated that the predominant cellular source of cfDNA was neutrophils. Whole blood transcriptome analysis also revealed neutrophil activation in NMOSD. In addition, enhanced NETosis induction was observed with NMOSD-derived sera, and efficient pharmacologic inhibition of NETosis with dipyridamole was observed. DISCUSSION: Our study highlights the previously unrevealed role of cfDNA predominantly released by neutrophil in the induction of IFN-1 signature in NMOSD and further indicate a novel pharmacologic target in NMOSD.
Indexed as
Cell-Free Nucleic AcidsNeuromyelitis OpticaHumansInterferonsLeukocytes, MononuclearNeutrophilsCell-Free Nucleic AcidsInterferons
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