ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

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

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO581

Role of Interferon-Gamma in Cyst Formation After AKI

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Smith, Morgan E., The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Ahmed, Ummey Khalecha Bintha, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Hopp, Katharina, University of Colorado Anschutz Medical Campus Department of Medicine, Aurora, Colorado, United States
  • Zimmerman, Kurt, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
Background

Acute kidney injury (AKI) is known to accelerate cystogenesis in conditional ciliopathy (Ift88) mice. Our lab previously showed that genetic deletion of adaptive immune cells significantly reduced cystic disease in Ift88 mice after AKI. Additionally, using single-cell RNA sequencing, we found that T cells isolated from conditional Ift88 mice after AKI had enriched expression of the cytokine interferon-gamma (IFN-γ). Based on these data, we hypothesize that T-cell-derived IFN-γ is a significant contributor to the accelerated cystogenesis that is seen following AKI in ciliopathy mice.

Methods

To test this hypothesis, we crossed conditional Ift88 mice to mice lacking IFN-γ. At 8 weeks of age, we induced loss of Ift88 and primary cilia through tamoxifen injection followed by administration of folic acid to induce AKI at 11-12 weeks of age; sodium bicarbonate solution was used as a vehicle-only control. Kidneys were harvested 56 days post-injury and cystic severity was measured by quantifying cystic index. We also analyzed changes in immune cell populations at the same time point using flow cytometry.

Results

Analyses of cyst severity 56 days post AKI indicate that conditional Ift88 IFN-γ knockout mice had a significant reduction in the severity and number of renal cysts compared to conditional Ift88 IFN-γ control mice. Analysis of flow cytometry data indicates a correlative reduction in the number of kidney resident macrophages and neutrophils in the conditional Ift88 IFN-γ knockout AKI mice compared to conditional Ift88 IFN-γ control AKI mice.

Conclusion

Collectively, our data indicate that T-cell-derived IFN-γ is a major contributor to accelerated cystic disease that is observed in conditional Ift88 mice post AKI. Ongoing studies are addressing the specific T cell subset involved in injury-accelerated disease and the potential mechanism through which IFN-γ accelerates cystic disease in conditional Ift88 mice following AKI.

Funding

  • NIDDK Support