Document resource
Objectives Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and immune dysregulation. Regulatory T cells (Tregs), defined by CD4 and FoxP3 expression, are critical for maintaining immune tolerance. However, whether their homeostasis or function is impaired in SLE remains unclear. This study investigated the phenotypic and functional alterations of Tregs in SLE and their association with disease activity.Methods Peripheral blood mononuclear cells from 51 SLE patients and 21 healthy controls (HCs) were analyzed by flow cytometry. CD4+FoxP3+ Tregs were evaluated for expression of inhibitory receptors (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT). To assess Treg plasticity, we examined the expression of lineage-associated transcription factors (T-bet, GATA3, RORrt) and cytokines (IFN-r, IL-4, IL-17A) following PMA/ionomycin stimulation. Correlations with disease activity, measured by SLEDAI-2K, were determined.Results The frequency of CD4+FoxP3+ Tregs was significantly higher in SLE patients compared with HCs (p = 0.002). Tregs from SLE patients exhibited increased expression of PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT (all p < 0.05). Upon stimulation, SLE Tregs showed elevated proportions of IFN-r+ and IL-17A+ cells (p = 0.032 and < 0.001, respectively), along with increased GATA3+ and RORrt+ expression (p < 0.001 and 0.002). Importantly, both total CD4+FoxP3+ Treg frequency and PD-1+ Tregs positively correlated with SLEDAI-2K scores (r = 0.386, p = 0.005; r = 0.323, p = 0.021).Conclusions SLE is associated with an expanded but functionally dysregulated Treg population, characterized by enhanced inhibitory receptor expression and acquisition of proinflammatory features. These abnormalities correlate with disease activity, highlighting Treg dysfunction as a potential biomarker and therapeutic target in SLE.