The left side shows a kidney with Th17 and gamma delta T cells producing IL-17A. IL-17A binds to IL-17RA and IL-17RC receptors on renal tubular epithelial cells, increasing tPA production. The right side shows tPA interacting with LRP1 on the epithelial cells, leading to ERK activation. This process reduces epithelial apoptosis and tubular injury, preserving kidney function.
IL-17–mediated antifungal host defense: from barrier immunity to renal epithelial protection. Following fungal dissemination to the kidney during systemic candidiasis, IL-17 produced predominantly by renal γδ T cells signals through IL-17RA/IL-17RC on renal tubular epithelial cells to induce tPA. Choi and colleagues identify the tPA–LRP1 axis as a downstream molecular effector of IL-17–dependent epithelial protection. Engagement of LRP1 by either catalytically active or inactive tPA activates an ERK1/2-dependent pro-survival signaling cascade, thereby limiting tubular epithelial apoptosis and injury while preserving renal function independently of fungal clearance. Together with earlier work demonstrating that epithelial-intrinsic IL-17 signaling promotes renal tubular epithelial survival during systemic candidiasis, these findings establish the renal epithelium as an active participant in antifungal host defense and illustrate how IL-17 integrates antifungal resistance with preservation of organ integrity. The illustration was created with Created in BioRender Lionakis, M. (2026) https://BioRender.com/5u8q254.