CXCL11 impairs the function of regulatory T cells in lupus patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Defects in the regulatory T cells (Treg cells) play a key role in breaking immune tolerance in SLE patients. This study investigates the causes of impaired Treg cell function in SLE patients. Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4⁺ T cells and plasma cytokine levels. Treg cells and naïve CD4⁺ T cells from healthy individuals were isolated, cultured under various conditions, and analyzed for phenotype and signal transduction mechanisms using flow cytometry, RT-qPCR, Western blotting, and calcium signaling assays. In SLE patients, the proportion of CD4⁺CD25⁺Foxp3⁺ and CD4⁺Foxp3⁺ Treg cells decreased. Plasma CXCL11 levels were elevated in lupus patients. CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity. CXCL11 impaired immune function and inhibited Treg cell differentiation. We present a novel pathological pathway in SLE, wherein CXCL11 impedes the immunosuppressive functions of Treg cells.