{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:13:01Z","timestamp":1792109581782,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Regulatory T cell (Treg)\u2010derived extracellular vesicles (EVs) represent a contact\u2010independent mechanism by which Tregs suppress dysregulated immune responses. These EVs carry diverse immunomodulatory molecules, including CD73, an ectoenzyme that hydrolyses AMP into adenosine. Adenosine subsequently acts as a potent immunosuppressive mediator that inhibits effector CD4\u207a T cell activation and controls pathological inflammation. Periodontitis is a highly prevalent inflammatory disease characterised by the accumulation of IL\u201017A\u2010expressing CD4\u207a T cells in response to dysbiotic oral bacterial biofilms, ultimately leading to RANKL\u2010mediated alveolar bone resorption and tooth loss. We tested the hypothesis that CD73\u207a Treg\u2010derived EVs, isolated from Tregs induced with polarising cytokines in the presence of retinoic acid, could limit inflammation and prevent alveolar bone loss in periodontitis. Our findings demonstrate that Tregs induced with polarising cytokines in the presence of retinoic acid express high levels of CD73 and secrete adenosine\u2010producing suppressive CD73\n                    <jats:sup>+<\/jats:sup>\n                    EVs. Furthermore, local administration of these CD73\u207a Treg\u2010derived EVs in a murine periodontitis model reduced activated CD4\u207a T cell infiltration, decreased IL\u201017A and RANKL expression, and attenuated osteoclast\u2010mediated alveolar bone loss. In conclusion, retinoic acid\u2010induced Treg\u2010derived EVs suppress CD4\u207a T cell\u2010driven inflammation and ameliorate periodontitis, at least in part through CD73\/adenosine\u2010dependent immunomodulatory mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70118","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T03:26:28Z","timestamp":1751858788000},"source":"Crossref","is-referenced-by-count":20,"title":["Induced Treg\u2010Derived Extracellular Vesicles Suppress CD4\n                    <sup>+<\/sup>\n                    T\u2010Cell\u2010Mediated Inflammation and Ameliorate Bone Loss During Periodontitis Partly Through CD73\/Adenosine\u2010Dependent Immunomodulatory Mechanisms"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-3999","authenticated-orcid":false,"given":"Carolina","family":"Rojas","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Periodontal, Faculty of Dentistry Universidad de Chile  Santiago Chile"},{"name":"Centro de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica, Faculty of Medicine Universidad de Los Andes  Santiago Chile"},{"name":"Faculty of Dentistry Universidad de los Andes  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4283-7269","authenticated-orcid":false,"given":"Michelle","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Periodontal, Faculty of Dentistry Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-6372","authenticated-orcid":false,"given":"Luis","family":"Gonz\u00e1lez\u2010Osuna","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Periodontal, Faculty of Dentistry Universidad de Chile  Santiago 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