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

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.