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Abstract: FR-PO981

CD206 Positive Renal Resident Macrophages Are Associated with Cyst Progression in a Juvenile-Induced Cilia Mutant Mouse Model

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Li, Zhang, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Zimmerman, Kurt, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Mrug, Michal, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Yoder, Bradley K., University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Polycystic kidney disease (PKD) is one of the most common inherited genetic renal diseases. Abnormalities in the structure or function of primary cilia are one cause of kidney cyst growth in animal models of PKD and human patients, but the mechanism of how primary cilia regulate cystogenesis is largely undefined. Recent data suggests that macrophages are associated with cyst formation in PKD; however, the contribution of specific macrophage subsets in promoting renal cyst formation and how this is related to ciliary dysfunction and cyst progression is unknown.

Methods

To address the involvement of cilia and macrophage subtypes in cyst formation, our lab utilized an inducible cilia deletion mouse model by conditionally disrupting the Ift88 gene. Macrophage populations were analyzed in both wild type and cilia mutant backgrounds as well as in human autosomal dominant PKD (ADPKD) patients with end-stage renal disease via immunofluorescence microscopy and flow cytometry at different time points following cilia loss.

Results

Our mouse data indicate that there is a predominant subset of renal resident macrophages expressing CD206 in juvenile WT mice and that the number of CD206+ macrophages decreases rapidly as the mice mature into adulthood. However, in conditional cilia deficient mice, induction of cilia loss in juvenile stages leads to persistently elevated numbers of CD206+ macrophages compared to control mice. Moreover, our data show that in the juvenile period the severity of cyst formation is associated with the time of cilia deletion. Early induction of cilia loss (e.g. P3), coincides with greater number of CD206+ macrophages and increased cyst severity compared to induction at later ages (e.g. P7). Preliminary analysis of kidneys from ADPKD patients shows increased numbers of CD206+ macrophages compared to normal human kidneys.

Conclusion

These data suggest that CD206+ macrophages are involved in renal cystogenesis in human patients and mouse models of renal cyst formation.

Funding

  • NIDDK Support