title: Interleukin-15 is a major regulator of the cell-microenvironment interactions in human renal homeostasis.
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.
authors.affiliation: Inserm UMR 1014, Hôpital Paul Brousse, Université Paris-Sud P11,Villejuif Cedex, France. julien.giron-michel@inserm.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Giron-Michel
authors.forename: Sandy
authors.initials: S
authors.lastname: Azzi
authors.forename: Silvano
authors.initials: S
authors.lastname: Ferrini
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Pierre
authors.initials: P
authors.lastname: Eid
authors.forename: Bruno
authors.initials: B
authors.lastname: Azzarone
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015820:Cadherins / Q000096:biosynthesis; D060833:Cellular Microenvironment; D058750:Epithelial-Mesenchymal Transition; D006084:Graft Rejection; D006706:Homeostasis; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism*; D007668:Kidney / Q000502:physiology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014411:Neoplastic Stem Cells
chemical_list: D015703:Antigens, CD; D015820:Cadherins; C569274:IL15 protein, human; D039001:Integrin alpha Chains; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; C091367:alpha E integrins