Interleukin-15 is a major regulator of the cell-microenvironment interactions in human renal homeostasis |
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| Authors: | Julien Giron-Michel Sandy Azzi Silvano Ferrini Salem Chouaib Giovanni Camussi Pierre Eid Bruno Azzarone |
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| Affiliation: | 1. Inserm UMR 1014, Hôpital Paul Brousse, Université Paris-Sud P11,Villejuif Cedex, France;2. Inserm UMR 1016, CNRS-UMR8104, Institut Cochin, Université Paris Descartes, Paris, France;3. Laboratory of Immunotherapy, National Cancer Research Institute, Genoa, Italy;4. INSERM UMR 753, Institut Gustave Roussy (IGR), Villejuif, France;5. Molecular Biotechnology Center, University of Turin, Italy;6. G. Gaslini Istitute, Genoa, Italy |
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| Abstract: | Experiments in IL-15?/? and IL-15Rα?/? mice show that intra-renal IL-15, through IL-15Rα behaves as an epithelial survival factor. Recent data highlight new functions of IL-15 in renal homeostasis mediated by IL-15Rγ (CD132). Indeed, in CD132+ renal epithelial tubular cells IL-15 preserves E-cadherin expression inhibiting epithelial-mesenchymal transition (EMT). By contrast, during allograft rejection, the increased intra-graft IL-15 expression favors tubular destruction facilitating the intraepithelial recruitment of CD8 T cells expressing the E-cadherin ligand CD103. In renal cancer, loss of CD132 by epithelial cells defines a tumoral microenvironment where IL-15 triggers E-cadherin down-regulation and EMT. Finally, in CD132+ renal cancer stem cells IL-15 induces the generation of non-tumorigenic epithelial cells sensitive to cytotoxic drugs. These findings are discussed in the light of IL-15-based immunotherapy for renal cancer. |
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