Renal cells express a functional interleukin-15 receptor Academic Article uri icon

abstract

  • Background. 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 bgc subunits (IL-2/15Rbgc) and a unique high-affinity a-chain responsible for IL-15 specificity. Methods. The cDNA of IL-15Ra 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-g (IFN-g), and mRNA and protein levels of IL-15R were determined. Jak–STAT tyrosine phosphorylation was assayed following IL-15 exposure. Results. The full-length a-chain mRNA bearing exons 1–7 is expressed in TEC. IL-15Ra protein was detected on intact cells by flow cytometry and in extracts of human and mice renal cells using a specific anti-IL15Ra 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-g upregulated the a-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). Conclusions. 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.

publication date

  • January 1, 2005