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

Cytokine Growth Factor Rev. 2013 Feb;24(1):13-22. doi: 10.1016/j.cytogfr.2012.08.006. Epub 2012 Sep 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cadherins / biosynthesis
  • Cellular Microenvironment
  • Epithelial-Mesenchymal Transition
  • Graft Rejection
  • Homeostasis*
  • Humans
  • Integrin alpha Chains / metabolism
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Interleukin-15 / metabolism*
  • Interleukin-15 Receptor alpha Subunit / metabolism*
  • Kidney / physiology*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / metabolism
  • Mice
  • Mice, Knockout
  • Neoplastic Stem Cells


  • Antigens, CD
  • Cadherins
  • IL15 protein, human
  • Integrin alpha Chains
  • Interleukin Receptor Common gamma Subunit
  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit
  • alpha E integrins