Renal cells express a functional interleukin-15 receptor

Abstract

Interleukin (IL)-15 is a pleiotropic cytokine known to be involved in graft rejection and to serve as a survival factor for leukocytes and epithelial cells, including renal cells. It utilizes a heterotrimeric receptor complex that consists of the IL-2 receptor betagammac subunits (IL-2/15Rbetagammac) and a unique high-affinity alpha-chain responsible for IL-15 specificity. The cDNA of IL-15Ralpha main mRNA product was isolated from primary human tubular epithelial cells (TEC) and sequenced. IL-15R expression in TEC and in murine renal tissue was demonstrated using western blotting, ligand binding and flow cytometry. TEC were activated with combinations of IL-15, IL-2 and interferon-gamma (IFN-gamma), and mRNA and protein levels of IL-15R were determined. Jak-STAT tyrosine phosphorylation was assayed following IL-15 exposure. The full-length alpha-chain mRNA bearing exons 1-7 is expressed in TEC. IL-15Ralpha protein was detected on intact cells by flow cytometry and in extracts of human and mice renal cells using a specific anti-IL-15Ralpha antibody and by ligand-binding assay. The three subunits of the IL-15R were similarly expressed in cortex and medulla of mice kidney. Stimulation of TEC with IFN-gamma upregulated the alpha-chain while IL-2 and IL-15 had no effect on its expression. A short IL-15 stimulation of TEC induced tyrosine phosphorylation of the main IL-15 signalling molecules (Jak-1, Jak-3, STAT-3 and STAT-5). Our data demonstrate the presence of a functional IL-15 receptor in the kidney. Since renal cells produce IL-15, this cytokine may have an autocrine/paracrine regulatory role in the kidney.