{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:19Z","timestamp":1792789639246,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Heart Association","award":["25POST1361665"],"award-info":[{"award-number":["25POST1361665"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"award":["25POST1361665"],"award-info":[{"award-number":["25POST1361665"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neutrophil extracellular traps (NETs) are web-like structures comprising chromatin scaffolds decorated with cytotoxic granule proteins released during a specialized form of neutrophil cell death termed NETosis. Although NETs function as a critical antimicrobial defense mechanism, their dysregulation contributes significantly to the pathogenesis of systemic lupus erythematosus (SLE). In SLE patients, both excessive NET formation by proinflammatory low-density granulocytes (LDGs) and impaired NET clearance due to reduced or acquired DNase1\/DNase1L3 activity create a pathogenic cycle that amplifies autoimmune activation. NETs serve as both a source of autoantigens and an immunological amplifier, driving Type I interferon responses, complement activation, B cell autoimmunity, endothelial dysfunction, and thrombosis. Recent advances have identified circulating biomarkers of NETosis, including cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and citrullinated histone H3, that correlate with SLE disease activity and organ involvement. Emerging therapeutic strategies targeting NETosis pathways, including peptidylarginine deiminase 4 (PAD4) inhibitors, recombinant DNase therapy, and complement modulators, show promise across preclinical studies and selected early clinical investigations. This comprehensive review synthesizes current mechanistic understanding of NET biology in SLE, examines the complex interplay between NETosis and innate\/adaptive immunity, evaluates clinical implications for diagnosis and prognosis, and critically assesses translational opportunities and remaining challenges in developing NETosis-targeted interventions for this devastating autoimmune disease.<\/jats:p>","DOI":"10.3390\/ijms27198530","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:16:28Z","timestamp":1790244988000},"page":"8530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Neutrophil Extracellular Traps (NETosis) in Systemic Lupus Erythematosus: Molecular Mechanisms, Pathogenic Roles, Diagnostic Biomarkers, and Emerging Therapeutic Strategies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-2044","authenticated-orcid":false,"given":"Gokul","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Health Care, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115738","DOI":"10.1016\/j.isci.2026.115738","article-title":"From pathogenesis to precision medicine in systemic lupus erythematosus: Emerging biomarkers and targeted interventions","volume":"29","author":"Lan","year":"2026","journal-title":"iScience"},{"key":"ref_2","first-page":"17","article-title":"Inherently inapt: The role of innate immunity in systemic lupus erythematosus pathogenesis","volume":"4","author":"Vital","year":"2025","journal-title":"Rare Dis. 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