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Abstract: TH-PO646

Adult Renal Stem/Progenitor Cells Exert Immunomodulatory Activity on T Regulatory Cells and Double Negative T Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

  • Sallustio, Fabio, University of Bari, Bari, Italy
  • Curci, Claudia, University of Bari, Bari, Italy
  • Chaoul, Nada, University of Bari, Bari, Italy
  • Picerno, Angela, University of Bari, Bari, Italy
  • Franzin, Rossana, University of Bari, Bari, Italy
  • Stasi, Alessandra, University of Bari, Bari, Italy
  • Divella, Chiara, University of Bari, Bari, Italy
  • Pontrelli, Paola, University of Bari, Bari, Italy
  • Gallone, Anna, University of Bari, Bari, Italy
  • Pertosa, Giovanni B., University of Bari, Bari, Italy
  • Castellano, Giuseppe, University of Bari, Bari, Italy
  • Gesualdo, Loreto, University of Bari, Bari, Italy
Background

Several studies show the active role of Adult Renal Stem/Progenitor Cells (ARPCs) in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. The aim of our study was to investigate the immunomodulatory properties of ARPCs on human T cells.

Methods

Human Peripheral Blood Mononuclear Cells (PBMCs) of healthy subjects were activated through incubation with Concanavalin A for 24h. ARPCs were activated by triggering TLR2 for 24h with Lipoteichoic acid (LTA) and co-cultured with T cells. Cell proliferation was measured by MTT cell viability assay. Phenotypic characterization of T cells was performed by flow cytometry. The relative expression levels of 36 cytokines of T cells and ARPCs, alone and in co-culture, were determined by Human Cytokine Proteome Array.

Results

TLR2-activated-ARPCs were able to decrease T cell proliferation after 24h of co-culture (p=0.017). In order to investigate changes in subset of T cell populations, we co-cultured PBMCs with activated ARPCs for short (5 days) and long period (15 days) of time. ARPCs did not affect CD3+CD8+ nor CD3+CD4+ T cells. Instead, we observed a significant decrease of Tregs (p<0.001) and CD3+CD4-CD8- DN T cell (p<0.0001) subpopulations after 5 and 15 days. Not significant effects were shown when T cells were co-cultured with renal proximal epithelial cells. Finally, by proteome array we identified cytokines secreted by ARPCs responsible for the immunomodulatory effect. SERPIN-E1, MIF, IL-8 and IL-6 were significantly up-regulated in the supernatant of T cells cocultured for 24h with TLR2-activated ARPCs, while were not present in supernatant of T cells alone.

Conclusion

Our data showed that ARPCs can regulate immune response by inducing T cell modulation through the TLR2 engagement. Interestingly,
ARPCs lead to down-regulation of Tregs and DN T cells, which are involved in the balance between immune tolerance and autoimmunity. Moreover, we identified four cytokines with a key role in this system. These findings can help to clarify the role of ARPCs in immunomodulation and could be translated to potential clinical treatment.

Funding

  • Government Support - Non-U.S.