CXCR6+ T cells promote apoptosis and necroptosis in proximal tubules during AKI-to-CKD transition - PubMed
6 hours ago
- #Acute Kidney Injury
- #Chronic Kidney Disease
- #Tubular Cell Death
- Acute kidney injury (AKI) can progress to chronic kidney disease (CKD) via maladaptive repair, involving tubular atrophy, inflammation, and fibrosis.
- Programmed cell death, such as apoptosis and necroptosis, drives proximal tubule (PT) loss, with immune infiltration playing a key but incompletely understood role.
- In a mouse model of maladaptive repair, injured kidneys showed PT loss, expansion of injured PT subsets, and late-stage T cell accumulation.
- Apoptotic and necroptotic signaling pathways were upregulated in VCAM1+ PT cells, with macrophage-derived Cxcl16 recruiting Cxcr6+ T cells via the CXCL16-CXCR6 axis.
- Genetic deletion of Cxcr6 reduced T cell accumulation, cytotoxic effects, and activation of apoptotic (cleaved caspase-3, Bax) and necroptotic (MLKL, phospho-MLKL) signaling in PT cells.
- Cxcr6-/- mice exhibited preserved PT differentiation, reduced fibrosis, and improved renal function, suggesting Cxcr6+ T cells as mediators of immune-driven tubular cell death.
- Targeting the CXCL16-CXCR6 axis may mitigate tubular injury and slow AKI-to-CKD progression, offering potential therapeutic strategies.