MO276: Renal Tubular CD24 Upregulation Aggravates Folic Acid-Induced Acute Kidney Injury Through Inhibition of Regulatory T Cells in Mice

Abstract

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a sialoglycoprotein which is induced during tissue damage and is not expressed in matured renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. METHOD A single i.p. injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. RESULTS FA-AKI induced the expression of CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. Renal and systemic IL-33 were upregulated in both groups. However, it was more pronounced in FA-AKI CD24-/- animals. FA-AKI CD24-animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice demonstrated increased expression of tubular pro-apoptotic (activated caspase 3) and decreased anti-apoptotic (Bcl-xL) proteins compared with WT animals. Administration of anti CD24 antibody to FA-AKI mice attenuated the decrease in renal function and ameliorated the histological injury in comparison with untreated animals. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. CONCLUSION During AKI, upregulation of CD24 promotes renal inflammation through inhibition of Tregs infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove as a target for future therapies in AKI.