Interleukin-15 is a major regulator of the cell-microenvironment interactions in human renal homeostasis

Julien Giron-Michel, Sandy Azzi, Silvano Ferrini, Salem Chouaib, Giovanni Camussi, Pierre Eid, Bruno Azzarone

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalCytokine and Growth Factor Reviews
Volume24
Issue number1
DOIs
Publication statusPublished - Feb 2013

Keywords

  • CD132
  • IL-15
  • IL-15Rα
  • Renal cancer
  • Renal cancer stem cells

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Biochemistry, Genetics and Molecular Biology(all)

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