Abstract: TH-PO114
Renal Tubular CD24 Upregulation Aggravates Folic Acid-Induced AKI Through Inhibition of T-Regulatory Cells in Mice
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Schwartz, Doron, Tel Aviv University, Tel Aviv, Israel
- Shashar, Moshe, Laniado Medical Center, Natania, Israel
- Schwartz, Idit F., Tel Aviv University, Tel Aviv, Israel
Background
Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein 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.
Methods
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 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. In contrast, renal and systemic IL-33 upregulation were augmented. CD24-/- FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function and attenuated histological injury. 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.