Abstract: SA-OR092
CD4 T Cells Promote Renal Cystic Disease
Session Information
- Pathogenesis of Cystic Kidney Diseases
November 09, 2019 | Location: 143, Walter E. Washington Convention Center
Abstract Time: 05:18 PM - 05:30 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- 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
The majority of renal cystic diseases are caused by mutations in proteins associated with primary cilia formation or function. Previous data indicate that mice with dysfunctional primary cilia have an enhanced innate immune response following injury and that these cells are required for accelerated cyst formation. Despite this knowledge, little work has studied the complementary adaptive immune system during injury induced cyst formation.
Methods
Herein, we set out to identify and determine the importance of adaptive immune cells, particularly CD4 T cells, during injury induced rapid cyst formation in conditional Ift88 mice (here after referred to as cilia mutant mice) and in the Ift88Orpk and adult induced conditional Ift88 slowly progressive models of cystic disease.
Results
Our data show that the number of T cells, including CD4, CD8 and double negative (DN) T cells, are increased in injured cilia mutant mice compared to controls. In addition, we show that the number of CD4, CD8, and DN T cells are also increased in the Ift88Orpk and adult induced, non-injured conditional Ift88 mouse models of slow cystogenesis. Further subtyping of CD4 T cells in these models shows that the number and percentage of Foxp3+ Tregs is increased in all 3 models of cystic disease compared to their respective controls. To test our hypothesis that adaptive immune cells are promoting cystic disease, we crossed our cystic mouse models to RAG1-/- mouse that lack all adaptive immune cells. Our data indicate that loss of adaptive immune cells reduces cyst formation in the rapid injury-induced model of cystogenesis but not in the slowly progressive models. To test the hypothesis that CD4 T cells were the adaptive immune cell type driving rapid cystogenesis following injury in cilia mutant mice, we injected conditional Ift88 and Pkd2 mice with an IgG or CD4 depleting antibody. Our data indicate that CD4 depletion reduces renal cystogenesis in both mouse models. Finally, analysis of human patients indicate that the number of Tregs is increased in autosomal dominant polycystic kidney disease patients compared to controls.
Conclusion
Our results suggest that CD4 T regulatory cells promote cystic kidney disease.
Funding
- NIDDK Support