ArticleScientific reports2020
Cellular uptake of extracellular nucleosomes induces innate immune responses by binding and activating cGMP-AMP synthase (cGAS).
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Rational modulation of immune mechanisms synergizes the anti-tumor effects of targeted radiation therapy in pre-clinical models.Frontiers in immunology · 2026Article
- Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis.Current issues in molecular biology · 2025Review
- Association between extracellular DNA levels, markers of inflammation and left ventricular mass index in children with chronic kidney disease.Scientific reports · 2025Observational
- Endocytosis and non-canonical autophagy mediate extracellular histones cytotoxicity in vascular models of sepsis.Frontiers in immunology · 2025Article
- The impact of circulating nucleosomes on inflammation in acute lung injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- Tumor Cells Transmit Drug Resistance via Cisplatin-Induced Extracellular Vesicles.International journal of molecular sciences · 2023Review
- Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.Cell insight · 2023Review
- Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy.Cancers · 2023Review
- STING in tumors: a focus on non-innate immune pathways.Frontiers in cell and developmental biology · 2023Review
- Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors.Biomedicines · 2022Review
- Nuclear cGAS: sequestration and beyond.Protein & cell · 2022Review
- cGAS‒STING signaling and function in metabolism and kidney diseases.Journal of molecular cell biology · 2021Review
- Nucleosomes enter cells by clathrin- and caveolin-dependent endocytosis.Nucleic acids research · 2021Article
- Targeting the DNA damage response in immuno-oncology: developments and opportunities.Nature reviews. Cancer · 2021Review
- The Trinity of cGAS, TLR9, and ALRs Guardians of the Cellular Galaxy Against Host-Derived Self-DNA.Frontiers in immunology · 2020Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleosome is the basic structural repeating unit of chromatin. DNA damage and cell apoptosis release nucleosomes into the blood circulatory system, and increased levels of circulating nucleosomes have been observed to be related to inflammation and autoimmune diseases. However, how circulating nucleosomes trigger immune responses has not been fully elucidated. cGAS (cGMP-AMP synthase) is a recently discovered pattern recognition receptor that senses cytoplasmic double-stranded DNA (dsDNA). In this study, we employed in vitro reconstituted nucleosomes to examine whether extracellular nucleosomes can gain access to the cytoplasm of mammalian cells to induce immune responses by activating cGAS. We showed that nucleosomes can be taken up by various mammalian cells. Additionally, we found that in vitro reconstituted mononucleosomes and oligonucleosomes can be recognized by cGAS. Compared to dsDNA, nucleosomes exhibit higher binding affinities to cGAS but considerably lower potency in cGAS activation. Incubation of monocytic cells with reconstituted nucleosomes leads to limited production of type I interferons and proinflammatory cytokines via a cGAS-dependent mechanism. This proof-of-concept study reveals the cGAS-dependent immunogenicity of nucleosomes and highlights the potential roles of circulating nucleosomes in autoimmune diseases, inflammation, and antitumour immunity.
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