MiR-223 within neutrophil axis promotes Th17 expansion by PI3K-AKT pathway in systemic lupus erythematosus

Abstract

Further investigation is required to determine the etiology of systemic lupus erythematosus (SLE). The aim of this study is to assess the presence of miR-223 within neutrophils in SLE and investigate its impact on the expansion of Th17 cells. Experiments were performed in MRL/lpr mice, which were divided into control and miR-223 knockdown (miR-223-) group. We assessed miR-223 expression within neutrophils and Th17 expansion in MRL/lpr mice and patients with SLE using RT-PCR, luciferase reporter assay, Elisa, flow cytometry analysis. Signaling pathway, RT-PCR and western blot were conducted to elucidate the mechanism by which miR-223 within neutrophils expands Th17. We initially identified miR-223 as a pivotal factor in the pathogenesis of SLE in both MRL/lpr mice and SLE patients. Subsequently, knockdown of miR-223 led to a significant reduction in Th17 expansion in MRL/lpr mice. Moreover, inhibition of miR-223 effectively attenuated the recruitment and activation of neutrophils in SLE. Furthermore, we found rb6-8c5 treatment alleviated lupus symptoms of MRL/lpr mice and reduce the level of Th17. Finally, we elucidated that neutrophils potentiate the induction of Th17 through the activation of thePI3K-AKT pathway mediated by miR-223 during SLE-associated Th17 expansion. MiR-223 within neutrophil axis contributes to Th17 expansion by PI3K-AKT pathway in SLE, and miR-223 could be a therapeutic target of SLE.