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Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects.

Created on 09 Sep 2026

Authors

Shushu Du, Wenqi Xu, Lili Zhao, Xiaofei Shi, Rongzeng Liu

Published in

Journal of cellular biochemistry. Volume 127. Issue 9. Pages e70124.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-system involvement, and its pathogenesis is complex, involving abnormalities of multiple immune cells and molecules. 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-tiered regulatory networks that control FOXP3 expression at the transcriptional, epigenetic, and post-translational 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)-2 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-dose IL-2 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.

PMID:
42709426
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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