Secukinumab: A new Hope for precision treatment of Acute kidney injury

Acute kidney injury (AKI) is a common clinical syndrome for which specific therapeutic measures are still lacking. This study reveals that activated Th17 cells are the primary source of the pro-inflammatory cytokine interleukin-17A (IL-17A) within the AKI immune microenvironment, and demonstrates that IL-17A likely serves as a key inflammatory mediator contributing to AKI injury. In several classic murine AKI models, IL-17A expression was significantly upregulated in renal tissues. Moreover, elevated serum IL-17A levels were confirmed in both clinical patients and mouse models compared to their respective controls. Functional studies showed that IL-17A knockout significantly improved renal function, attenuated histopathological damage such as tubular necrosis, and effectively preserved the integrity of the renal microvascular endothelium in mice. Comparative transcriptomic analysis of IL-17A knockout mice identified 13 key signaling pathways, including IL-17, cAMP, and PI3K-Akt, with Ptgs2, Il6, and Lcn2 being identified as critical downstream effector genes synergistically regulated by the IL-17A axis. In vitro experiments confirmed that rhIL-17A synergistically interacts with various injurious stimuli to significantly enhance the expression of the three key effector genes in HK-2 cells at both transcriptional and protein levels. More importantly, treatment with Secukinumab significantly reversed renal function impairment induced by multiple etiologies by suppressing the aberrant expression of these key downstream mediators, thereby downregulating the injury marker NGAL and effectively alleviating histopathological damage. Collectively, these results position the Th17/IL-17A axis as a shared pathogenic driver in AKI of diverse etiologies and identify Secukinumab as a compelling candidate for precision-targeted therapy in AKI.