{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:58:14Z","timestamp":1793174294679,"version":"4.5.0"},"reference-count":36,"publisher":"American Society for Clinical Investigation","issue":"13","funder":[{"name":"NIAMS\/NIH","award":["ZIA AR041199"],"award-info":[{"award-number":["ZIA AR041199"]}]},{"name":"NIAMS\/NIH","award":["ZIA AR041199"],"award-info":[{"award-number":["ZIA AR041199"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,9]]},"abstract":"<jats:p>\n                    Rheumatoid arthritis (RA) is characterized by synovial joint inflammation, cartilage damage, and dysregulation of the adaptive immune system. While neutrophil extracellular traps (NETs) have been proposed to play a role in the generation of modified autoantigens and in the activation of synovial fibroblasts, it remains unknown whether NETs are directly involved in cartilage damage. Here, we report a new mechanism by which NET-derived elastase disrupts cartilage matrix and induces release of membrane-bound peptidylarginine deiminase-2 by fibroblast-like synoviocytes (FLSs). Cartilage fragments are subsequently citrullinated, internalized by FLSs, and then presented to antigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Furthermore, immune complexes containing citrullinated cartilage components can activate macrophages to release proinflammatory cytokines. HLA-DRB1*04:01 transgenic mice immunized with NETs develop autoantibodies against citrullinated cartilage proteins and display enhanced cartilage damage. Inhibition of NET-derived elastase rescues NET-mediated cartilage damage. These results show that NETs and neutrophil elastase externalized in these structures play fundamental pathogenic roles in promoting cartilage damage and synovial inflammation. Strategies targeting neutrophil elastase and NETs could have a therapeutic role in RA and in other inflammatory diseases associated with inflammatory joint damage.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.139388","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T12:01:48Z","timestamp":1591099308000},"source":"Crossref","is-referenced-by-count":184,"title":["Neutrophil extracellular traps mediate articular cartilage damage and enhance cartilage component immunogenicity in rheumatoid arthritis"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-1464","authenticated-orcid":true,"given":"Carmelo","family":"Carmona-Rivera","sequence":"first","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-4572","authenticated-orcid":true,"given":"Philip M.","family":"Carlucci","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-5191","authenticated-orcid":true,"given":"Rishi R.","family":"Goel","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"James","sequence":"additional","affiliation":[{"name":"Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5592-5332","authenticated-orcid":true,"given":"Stephen R.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliff","family":"Rims","sequence":"additional","affiliation":[{"name":"Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Veterinary Resources, Office of the Director, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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