CD49f Expression in CD4 + T Cells and CD4 +  FoxP3 + Tregs Reveals Immune Dysregulation and Potential Diagnostic Value in Systemic Lupus Erythematosus

ABSTRACT This study aimed to characterise the expression and functional heterogeneity of CD49f across CD4+ T cell subsets in human peripheral blood, and to investigate alterations in regulatory T cells (Tregs) and CD4+ T cells in patients with systemic lupus erythematosus (SLE), together with their clinical relevance. A total of 43 newly diagnosed, treatment‐naïve SLE patients and 21 age‐ and sex‐matched healthy controls were enrolled. Peripheral blood mononuclear cells were analysed by flow cytometry to assess CD49f expression in CD4 + FoxP3+ Tregs and non‐Treg CD4+ T cells. Phenotypic and function‐related markers were compared between CD49f + and CD49f− subsets. IL‐10 production was evaluated as a functional readout in CD49f‐defined Treg subsets. Associations between CD49f‐related populations and clinical parameters were analysed, and receiver operating characteristic (ROC) curve analysis was performed to explore their potential clinical relevance. CD49f expression was higher in CD4 + FoxP3+ Tregs than in other CD4+ T cells. CD49f + CD4+ T cells exhibited increased CD226 and decreased CD45RA expression, consistent with an activated phenotype. CD49f + Tregs were enriched in the CD45RA‐FoxP3int subset and showed higher CD226 but lower GZMB and Helios expression, indicating attenuated suppressive phenotypic features. In healthy controls, CD49f + Tregs displayed significantly higher IL‐10 production than CD49f− Tregs, whereas this functional distinction was lost in SLE patients. The proportions of CD49f + subsets were significantly increased in SLE and correlated with multiple clinical indicators. ROC analysis revealed moderate discriminative performance of CD49f‐related subsets, with AUC values ranging from 0.640 to 0.786. In conclusion, CD49f identifies distinct phenotypic and functional states within CD4+ T cells and Tregs. CD49f + CD4+ T cells exhibit activation features, while CD49f + Tregs show phenotypic attenuation accompanied by functional heterogeneity that is preserved in health but disrupted in SLE. Increased CD49f expression in SLE reflects immune imbalance and suggests potential value as a cellular immunological marker rather than a standalone diagnostic tool.