Abstract: SA-PO1044
Systemic Immune Dysregulation in a Mouse Model of Oxalate Nephropathy
Session Information
- Pathology and Lab Medicine - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Bartolomaeus, Hendrik, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Wimmer, Moritz Immanuel, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Rauch, Ariana, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Anandakumar, Harithaa, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Reichel, Martin, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Knauf, Felix, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
- Wilck, Nicola, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background
Chronic kidney disease (CKD) is a leading cause of mortality and morbidity. Crystalline nephropathy induced by high oxalate is an established cause of CKD. CKD and crystal formation were shown to influence immune cell composition and gut microbiota. To investigate the impact of oxalate nephropathy on the immune system and the microbiome, high oxalate-fed mice were analyzed by flow cytometry and 16S sequencing.
Methods
To investigate the effects of oxalate we fed single housed C57BL6/N mice (n=7) a high oxalate diet for 10 days. Chow diet fed littermates served as healthy controls. Both groups were analyzed for immune cell composition (flow cytometry) of the spleen, kidney and small/large intestine (lamina propria immune cells [si/cLPL]) and bulk RNA sequencing of the kidney. Microbiota composition was analyzed by 16S sequencing.
Results
Mice fed a high oxalate diet demonstrated hyperoxaluria and increased kidney injury as measured by plasma creatinine concentration. Furthermore, we observed a significant reduction in body weight. Bulk RNA sequencing revealed a prominent inflammatory signature of the kidney, including increased classical damage markers (Lcn2, Havcr1), as well as genes enriched for Th17 differentiation pathway. Flow cytometry analysis identified more than 100 dysregulated immune subpopulations in the kidney. Furthermore, we detected a pronounced inflammatory response in the spleen and the intestine. Interestingly, type 17 T cells (IL-17A+ and RORgt+) within conventional T helper and regulatory T cells were the main and overlapping phenotypic drivers across different organs, namely the kidney, small and large intestine. Compared to the immune system, the microbiome only showed small scale taxonomic shifts (increase of 4 vs. decrease of 9 operational taxonomic units).
Conclusion
Our in-depth immune phenotyping uncovers a pronounced inflammatory signature across several organs (intestine, spleen and the kidney). Our study provides a comprehensive description of immune cell alterations and serves as a valuable resource for the scientific community.