ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO101

Superagonistic CD28 Protects Against Renal Ischemia Injury-Induced Fibrosis Through a Regulatory T Cell Expansion Dependent Mechanism

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Liang, Yiran, Zhongshan Hospital, Fudan University, Shanghai, China
  • Fang, Yi, Zhongshan Hospital, Fudan University, Shanghai, China
  • Ding, Xiaoqiang, Zhongshan Hospital, Fudan University, Shanghai, China
Background

To investigate the potential protective effect of superagonistic CD28 (CD28sa) on the chronic outcome post acute kidney ischemia injury and related mechanism.

Methods

Male C57BL/6N mice were treated with CD28sa via peritoneal injection 6 days before the induction of ischemia renal injury (IRI), IRI was induced by bilateral clamping of renal pedicles for 35 min followed by reperfusion. 7, 14 and 28 days after the IRI surgery, mice were euthanized and specimens were harvested. The role of regulatory T cells (Tregs) expansion in the renal protection conferred by CD28sa treatment was examined using an anti-CD25 antibody (PC61) to partially deplete Tregs. The chronic pathological outcome of mice renal was identified by Masson staining, Sirius Red staining and renal fibrosis related extracellular matrix immunochemistry (IHC) staining.

Results

CD28sa treatment significantly promoted the percentage of Tregs in the spleen, kidney and peripheral blood 24 h after the IRI. Serum creatinine level was remitted by CD28sa administration in a short term (7 days). Histological analysis indicated that CD28sa attenuated renal tubular damage. CD28sa also attenuated the extracellular matrix deposition in the renal medulla site 28 days after IRI. Immunoblot showed that Collagen IV expression of kidney was lowered by CD28sa administration 28 days after IRI. Immune cells in kidneys from CD28sa pre-treated IRI mice were characterized by an increased percentage of Tregs and MHCII+CD11c+ dendritic cells, significantly decreased Th17 cells and also increased secretion of Tregs effector cytokine IL-10. CD28sa pretreatment also resulted in less cells apoptosis and less oxidative stress of renals marked by less TUNEL and 8-OHdg positive stained cells. On the other hand, the renal protection bestowed by CD28sa was abolished by PC61 administration.

Conclusion

CD28sa alleviated renal chronic outcome after the acute ischemic injury, probably associated with the inchoate up-regulation of Treg cells.

Funding

  • Government Support - Non-U.S.