Interleukin-17 A and diabetic kidney disease: emerging evidence on its pathogenic role and targeted modulation

Diabetic kidney disease (DKD), a significant microvascular complication of diabetes, is a multifactorial condition and a primary cause of both chronic kidney disease (CKD) and end-stage renal disease (ESRD). Interleukin-17 A (IL-17 A), an essential pro-inflammatory cytokine, is gaining recognition for its role in the development of DKD, highlighting its potential as a new therapeutic target. The pathogenic roles of IL-17 A may be mediated through several mechanisms, including the amplification of inflammatory responses, disruption of immune homeostasis, promotion of renal fibrosis, inhibition of mitochondrial autophagy, and perturbation of gut microbiota balance. Importantly, IL-17 A appears to exert both deleterious and potentially protective effects, reflecting a complex regulatory role in disease progression. However, the current evidence supporting these dual functions remains limited and context-dependent. Comparative analyses with other cytokines, such as IL-6, IL-1β, TNF-α, IL-22, and other IL-17 family members, are needed to position IL-17 A within the broader cytokine network and clarify its relative pathogenic and therapeutic significance. In this review, we critically examine the mechanistic basis of IL-17 A-mediated therapeutic strategies for DKD, drawing on recent advances from both established and emerging research. Furthermore, we identify key unresolved questions and propose future directions to guide ongoing and prospective investigations in this evolving field.