{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:46:44Z","timestamp":1792896404163,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018554","name":"Science and Technology Program of Gansu Province","doi-asserted-by":"publisher","award":["23JRRA1510"],"award-info":[{"award-number":["23JRRA1510"]}],"id":[{"id":"10.13039\/501100018554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neutrophil extracellular traps (NETs) significantly contribute to rheumatoid arthritis (RA) pathogenesis, though their exact mechanisms remain unclear. In this research, we explored how NETs influence RA development through the PANoptosis core molecule AIM2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Enzyme\u2010linked immunosorbent assay and Quant\u2010iT Pico Green measured AIM2 and cell\u2010free DNA (cfDNA) levels in synovial fluid. Immunohistochemistry examined the levels of AIM2 in synovial tissues. In\u00a0vitro, the CCK\u20108 assay evaluated cell proliferation. Western blot detected the expression changes of AIM2, PANoptosis\u2010related proteins, and NF\u2010\u03baB pathway\u2010related proteins. Real\u2010time quantitative PCR measured mRNA levels of IL\u20101\u03b2, IL\u201018, and IL\u20106. Immunofluorescence quantified AIM2, Caspase\u20108, GSDMD, and p\u2010MLKL fluorescence intensity and cfDNA\/AIM2 co\u2010localization. An AIM2\u2010silenced cell model was established to examine changes in the AIM2, PANoptosis\u2010related proteins, and NF\u2010\u03baB pathway\u2010related proteins (Western blot), fluorescence intensity (IF), inflammatory cytokine transcription (RT\u2010qPCR), and RA\u2010FLS migration (scratch and transwell assays).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results showed an increase in AIM2 expression in RA synovial fluid and tissues, which correlates with both cfDNA high levels and clinical disease activity scores. In\u00a0vitro, in RA fibroblast\u2010like synoviocytes (RA\u2010FLSs), NETs elevated AIM2 and PANoptosis\u2010related protein levels, activated the NF\u2010\u03baB signaling pathway, and enhanced the release of inflammatory cytokines. Treatment with DNase1 and AIM2 silencing resulted in lower levels of PANoptosis proteins and AIM2, inhibited NF\u2010\u03baB signaling, and decreased cytokine production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first time exploring the pathogenic mechanism of NETs\u2010induced PANoptosis in RA, and targeting AIM2 may represent a potential new therapeutic approach for RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70452","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:01:51Z","timestamp":1770033711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neutrophil Extracellular Traps Induce\n                    <scp>PANoptosis<\/scp>\n                    and Inflammatory Responses in Fibroblast\u2010Like Synoviocytes of Rheumatoid Arthritis"],"prefix":"10.1111","volume":"29","author":[{"given":"Xing","family":"Zhang","sequence":"first","affiliation":[{"name":"The Second Hospital and Clinical Medical School Lanzhou University  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Ultrasound Medical Center, the Second Hospital and Clinical Medical School Lanzhou University  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Hospital and Clinical Medical School Lanzhou University  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Mao","sequence":"additional","affiliation":[{"name":"The Second Hospital and Clinical Medical School Lanzhou University  Lanzhou Gansu 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