Upregulated expression of STAT3/IL-17 in patients with systemic lupus erythematosus

Abstract

Elevated IL-17 levels with higher Th17 numbers are identified in systemic lupus erythematosus (SLE). STAT3 signaling plays a crucial role in the Th17 generation, and SOCS3 negatively regulates their formation. We investigated IL-17, STAT3, and SOCS3 expression, and analyzed their correlations to elucidate the regulatory mechanisms of IL-17 production in SLE. This study enrolled 32 patients, and venous mononuclear cells (MNCs) were isolated with further purification of CD4-positive T cells. IL-17 and SOCS3 levels were measured by real-time quantitative PCR, and pSTAT3/STAT3 expression was analyzed by immunoblot. Elevated IL-17 and SOCS3 levels were identified in lupus patients. There were higher IL-17 levels in lupus nephritis (class IV) than in SLE without renal involvement. Positive correlations were found between IL-17 levels and SOCS3 expression, lupus activity (SLEDAI-2K), or daily proteinuria. There were higher intensities of pSTAT3/β-actin and STAT3/β-actin in SLE, and a positive correlation between IL-17 expression and pSTAT3/β-actin or STAT3/β-actin intensity. Lupus nephritis (class IV) had higher STAT3/β-actin intensity than SLE without renal involvement. These results suggest upregulated STAT3/IL-17 expression in lupus patients. Such findings might facilitate the development of novel compounds and the application of existing therapeutics targeting the STAT3/IL-17 signal in SLE.