{"entity": "publication", "iuid": "09bd31d6e7984f7fa1e9d45891054a2f", "timestamp": "2026-08-25T13:39:38.430Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/09bd31d6e7984f7fa1e9d45891054a2f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/09bd31d6e7984f7fa1e9d45891054a2f"}}, "title": "NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-\u03b1 production in patients with SLE.", "authors": [{"family": "Georgakis", "given": "Spiros", "initials": "S"}, {"family": "Gkirtzimanaki", "given": "Katerina", "initials": "K"}, {"family": "Papadaki", "given": "Garyfalia", "initials": "G"}, {"family": "Gakiopoulou", "given": "Hariklia", "initials": "H"}, {"family": "Drakos", "given": "Elias", "initials": "E"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Makridakis", "given": "Manousos", "initials": "M"}, {"family": "Kontostathi", "given": "Georgia", "initials": "G"}, {"family": "Zoidakis", "given": "Jerome", "initials": "J"}, {"family": "Baira", "given": "Eirini", "initials": "E"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}, {"family": "Boumpas", "given": "Dimitrios T", "initials": "DT"}, {"family": "Sidiropoulos", "given": "Prodromos", "initials": "P"}, {"family": "Verginis", "given": "Panayotis", "initials": "P"}, {"family": "Bertsias", "given": "George", "initials": "G"}], "type": "journal article", "published": "2021-11-08", "journal": {"title": "JCI Insight", "issn": "2379-3708", "volume": "6", "issue": "21", "issn-l": null}, "abstract": "IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33-decorated NETs that stimulate robust IFN-\u03b1 synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. IL33-silenced neutrophil-like cells cultured under lupus-inducing conditions generated NETs with diminished interferogenic effect. Importantly, NETs derived from patients with SLE are enriched in mature bioactive isoforms of IL-33 processed by the neutrophil proteases elastase and cathepsin G. Pharmacological inhibition of these proteases neutralized IL-33-dependent IFN-\u03b1 production elicited by NETs. We believe these data demonstrate a novel role for cleaved IL-33 alarmin decorating NETs in human SLE, linking neutrophil activation, type I IFN production, and end-organ inflammation, with skin pathology mirroring that observed in the kidneys.", "doi": "10.1172/jci.insight.147671", "pmid": "34554930", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8663547"}, {"db": "pii", "key": "147671"}], "notes": [], "created": "2026-08-21T12:31:48.726Z", "modified": "2026-08-21T12:31:48.746Z"}