Abstract: TH-PO0574
Renal Progenitor Cells Can Modulate Inflammatory and Intestinal Immune Activation in IgAN
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Sallustio, Fabio, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Montenegro, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Picerno, Angela, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Giannuzzi, Francesca, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Cicirelli, Antonella, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Nigro, Alessio, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Papadia, Federica, Policlinic Hospital of Bari, Bari, Italy
- Ferrulli, Roberta, Policlinic Hospital of Bari, Bari, Italy
- Cimmarusti, Maria Teresa, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Stasi, Alessandra, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Di Leo, Vincenzo, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
- Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Apulia, Italy
Background
Recent investigations explored the complex ways in which adult renal progenitor cells (RPCs) impact renal disorders. RPCs have a variety of roles in kidney disorders, including immunological regulation, tissue regeneration, and renal homeostasis maintenance.
We isolated the RPCs from the urine of IgA Nephropathy (IgAN) patients and compared them with renal CD133- cells to identify genes and biological processes specifically activated in RPCs.
Methods
Urine-derived cells were collected from 5 IgAN patients and 5 Healthy Subjects (HS). RPCs were isolated, characterized for the CD133 and CD24 markers by cytofluorimetric analysis and separated from the CD133- portion by immunolabeling. RNA-sequencing was performed on both cell fractions from IgAN patients and HS. Differential analysis, Over Representation Analysis (ORA) and Gene set enrichment analysis (GSEA) were performed.
Results
We found 39 genes exclusively expressed in RPCs from IgAN patients, while 140 genes were specifically expressed in CD133- cells. Only 14 genes were shared by these two cell types. The ORA and GSEA analyses showed that RPCs modulate genes involved in immunomodulatory mechanisms only in IgAN, such as the regulation of leukocyte migration, T cell proliferation, T-reg cells, and response to molecules of bacterial origin (FDR 0.0238). Noteworthy, compared to CD133- cells, in RPCs of patients we found the downregulation of relevant genes involved in IgAN, such as IL6 (logFC -3.35, FDR 0.0002), CXCL1 (logFC -2.87, FDR 0.0178), CXCL8 (logFC -4.12, FDR 0.0007), whereas TNFRSF14 (HVEM or CD270), a receptor involved in the intestinal inflammation and mucosal immunity, was upregulated (logFC 2.67, FDR 0.0295). Our data showed that through the HVEM expression, RPCs can dampen gut-activated T and B cells that reach the kidney.
Conclusion
Our data suggest that in IgAN RPCs play a role in decreasing inflammatory and immunological triggering at the renal level. By better understanding the critical role of these cells in the complex pathophysiology of IgAN, novel treatment strategies aiming to slow down the progression of IgAN can be developed.
Funding
- Government Support – Non-U.S.