Expression of interleukin 13 receptor in glioma and renal cell carcinoma: IL13R alpha 2 as a decoy receptor for IL13

Glioma and renal cell carcinoma (RCC) cells express high affinity interleuk in 13 (IL13) binding sites, but only RCC cell proliferation was inhibited b y IL13. Both of these two cell types are IL2-receptor gammac chain-negative . We thus used these cell models to investigate the patterns of expression of IL13R alpha1, IL13R alpha2, and IL4R alpha chains and the role of IL13R alpha2 in the response to IL13. Using new specific antibodies and flow cyto metry, we observed a similar surface expression of IL4R alpha and IL13R alp ha1 chains in most RCC and glioma cells, whereas IL13R alpha2 was only pres ent on five of six glioma cell lines. In all glioma cell lines, the amount of IL13R alpha2 expression was 10 to 30 times higher than that of the two o ther chains. Although there was no surface or intracellular expression of I L13R alpha2, its mRNA was detected in three of seven RCC cell lines. The ex pression on RCC cells of IL13R alpha2 mRNA and/or that of high-affinity IL1 3 binding sites is not sufficient to predict IL13R alpha2 protein expressio n. Blocking experiments showed that IL4 and IL13 strongly inhibited RCC cel l proliferation through a unique receptor composed of IL4R alpha and IL13R alpha1 chains. Using RCC cells stably transfected with IL13R alpha2 cDNA, w e showed that the overexpression of IL13R alpha2 decreased the response to IL13 but not that to IL4. Our results demonstrate that IL13R alpha2 acts as a decoy receptor for IL13 and that it may exert a tight regulation of IL13 activity without impairing the IL4 response of the same cell target.