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In recent years, the role of the transcription factor Forkhead Box P3 (FOXP3) in SLE has attracted much attention. FOXP3, a crucial indicator of regulatory T cells (Tregs), is essential for maintaining immune tolerance and suppressing excessive immune responses. This review systematically elucidates the multi\u2010tiered regulatory networks that control FOXP3 expression at the transcriptional, epigenetic, and post\u2010translational levels. It further examines the specific phenotypic alterations and molecular mechanisms responsible for the dysregulation of Treg quantity, function, and stability within the SLE milieu, including factors such as interleukin (IL)\u20102 deficiency, cytokine storms, and epigenetic abnormalities. Building upon this foundation, the article explores a range of emerging therapeutic strategies targeting FOXP3 and Tregs as central elements, highlighting recent advances and clinical translation prospects in low\u2010dose IL\u20102 therapy, adoptive Treg cell transfer, and epigenetic drug interventions. Ultimately, we propose that the precise modulation and enhancement of Treg function to restore stable immune tolerance in SLE patients constitutes a novel therapeutic paradigm, transitioning from broad immunosuppression toward targeted immune modulation. This strategy holds significant promise for fundamentally improving the therapeutic landscape of this complex autoimmune disorder.<\/jats:p>","DOI":"10.1002\/jcb.70124","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:16:51Z","timestamp":1788895011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects"],"prefix":"10.1002","volume":"127","author":[{"given":"Shushu","family":"Du","sequence":"first","affiliation":[{"name":"Department of Immunology College of Basic Medicine and Forensic Medicine Henan University of Science and Technology Luoyang China"},{"name":"Qingpu Traditional Chinese Medicine Hospital Shanghai 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