{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:12:07Z","timestamp":1790014327056,"version":"4.0.1"},"reference-count":190,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"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:p>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with significantly accelerated atherosclerosis (AS) and increased cardiovascular risk. This review elucidates the complex immunopathological mechanisms through which SLE promotes AS, involving both innate and adaptive immune dysregulation. Aberrant activation of the type I interferon signaling pathway and dysfunctional neutrophil\/NETosis reciprocally amplify each other, forming a core upstream positive feedback loop. This loop accelerates atherosclerosis progression through multiple pathways, including driving endothelial dysfunction, promoting foam cell formation, and undermining plaque stability. Dysregulation of innate immune cells is prominent. Monocytes and macrophages exhibit altered polarization and impaired efferocytosis. Complement activation further exacerbates vascular injury. Within the adaptive immune system, T-cell subsets are imbalanced, promoting inflammation and AS progression. B cells and autoantibodies play dual roles. Although certain natural IgM antibodies may be protective, class-switched IgG autoantibodies often promote atherosclerosis. The role of B-cell activating factor (BAFF) and its inhibition in AS remains complex and context dependent. Animal models have been instrumental in dissecting these pathways, revealing interactions between lupus-like autoimmunity and atherogenic processes. Despite these advances, accurately assessing cardiovascular risk in SLE patients remains challenging, underscoring the need for SLE-specific risk prediction tools. Future directions should focus on identifying specific immune mechanisms, developing targeted immunomodulatory therapies, and establishing improved risk stratification strategies to enable early intervention and improve long-term outcomes for patients with SLE.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1766970","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:02:43Z","timestamp":1772607763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunopathogenesis of accelerated atherosclerosis in systemic lupus erythematosus: from innate and adaptive dysregulation to clinical implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Shirui","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Clinical Research Center for Metabolic and Cardiovascular Disease, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinme.2025.100509","article-title":"Challenges in the 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