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-PO677

Flt3 Inhibitor Attenuates Renal Injury in Adriamycin Nephropathy by Suppressing CD103+ DC-Mediated T Cell Activation

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Cao, Qi, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Chen, Titi, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Lee, Vincent W.S., The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Zheng, Guoping, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Wang, Yiping, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Harris, David C., The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
Background

In our previous study, CD103+ DCs were shown to play a pathogenic role via activation of CD8 T cells in Adriamycin nephropathy (AN), a model of focal segmental glomerulosclerosis. FMS-like tyrosine kinase 3 (Flt3) is a receptor which is highly and specifically expressed on tissue resident CD103+ DCs. To test the effect on renal injury of inhibition of Flt3 on CD103+ DCs, we used a selective Flt3 inhibitor (AC220) to treat mice with AN.

Methods

AN was induced in BALB/c mice, who were treated daily for 14 days with 10mg/kg AC220 or Vehicle (n=8/group) from day 7 after adriamycin, when AN was established. Renal functional and structural injury, as well as inflammatory cytokine expression and cell infiltration were assessed.

Results

The number of kidney CD103+ DCs, but not CD103- DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved renal function (creatinine clearance: 22.8±4.9 vs. 50.2±13.3 µl/min) and reduced structural renal injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines IL-1beta, IL-6 and TNF-a in kidney. AC220 treatment decreased infiltration of CD4 T cells, CD8 T cells and macrophages in kidney, and reduced inflammatory cytokine and cytotoxic molecule expression of kidney CD8 T cells in AN mice.

Conclusion

Flt3 inhibitor AC220 effectively reduced renal injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat chronic kidney disease.

Funding

  • Government Support - Non-U.S.