{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:15:40Z","timestamp":1782209740205,"version":"3.54.5"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>IL-1\u03b2 is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1\u03b2-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1\u03b2 secretion. The first objective of our study was to characterize IL-1\u03b2-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The second objective was to detect circulating IL-1\u03b2-positive MVs in JIA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS \u00b1 ATP. MV content was analyzed for the presence of IL-1\u03b2, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied <jats:italic>in vitro<\/jats:italic> by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. <jats:italic>In vivo<\/jats:italic>, MVs\u2019 ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1\u03b2-positive MVs were studied <jats:italic>ex vivo<\/jats:italic> in 10 active JIA patients using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>THP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1\u03b2 and bioactive TF. IL-1\u03b2-positive MVs expressed P2X7 receptor and released soluble IL-1\u03b2 in response to ATP stimulation <jats:italic>in vitro<\/jats:italic>. In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1\u03b2-positive MVs were detectable in plasma from 10 active JIA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MVs shed from activated macrophages contain IL-1\u03b2, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1228122","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T16:04:35Z","timestamp":1700755475000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Macrophage IL-1\u03b2-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic 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