RETRACTED: Soluble interleukin (IL)-15Rα is generated by alternative splicing or proteolytic cleavage and forms functional complexes with IL-15 (Retracted Article. See vol 286, pg 5934, 2011)

Interleukin 15 (IL-15) is a pleiotropic cytokine that is hardly detectable in biological fluids. Here, we show that IL-15 forms functional heterocomplexes with soluble high affinity IL-15 receptor alpha (IL-15R alpha) chain in mouse serum and cell-conditioned medium, which prevents IL-15 detection by ELISA. We also demonstrate that two soluble IL-15R alpha (sIL-15R alpha) sushi domain isoforms are generated through a novel alternative splicing mechanism within the IL-15R alpha gene. These isoforms potentiate IL-15 action by promoting the IL-15-mediated proliferation of the CTLL cell line and interferon gamma production by murine NK cells, which suggests a role in IL-15 transpresentation. Conversely, a full-length sIL-15R alpha ectodomain released by tumor necrosis factor-alpha-converting enzyme (TACE)-dependent proteolysis inhibits IL-15 activity. Thus, a dual mechanism of sIL-15R alpha generation exists in mice, giving rise to polypeptides with distinct properties, which regulate IL-15 function.