Two copies of the genes encoding the subunits of putative interleukin (IL)-4/IL-13 receptors, IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2, have been identified in rainbow trout (Oncorhynchus mykiss) and have complex patterns of expression and modulation.

摘要

Mammalian interleukin-4 (IL-4) and IL-13 are T helper type 2 (Th2) cytokines with pleiotropic functions in immunity. They signal through receptors containing IL-4Ralpha and IL-2Rgamma or IL-13Ralpha1. In addition, a decoy receptor, IL-13Ralpha2, is known to exist and modulates the function of IL-13. The existence of fish orthologues to mammalian IL-4 and IL-13 is still under debate. However, the receptor chains have been predicted in zebrafish, and we have previously cloned IL-2Rgamma and IL-13Ralpha2 in rainbow trout. In this study, we have cloned a further five novel trout IL-4/13 receptors. Thus, each of the IL-4Ralpha, IL-13Ralpha1 and IL-13Ralpha2 chains has two copies. The identities of the receptors is supported by homology analysis, characteristic domain structure, phylogenetic tree analysis and synteny analysis in zebrafish. However, the characteristic WSXWS motif of structural importance in mammalian type I cytokine receptors is missing in all fish IL-4Ralpha and IL-13Ralpha1 molecules. All the receptors have a characteristic domain structure that is similar to their mammalian counterparts except for IL-13Ralpha1b that has the N-terminal Ig domain missing. Since this Ig domain is a specific and critical binding unit for IL-13 but not for IL-4 signalling, its absence potentially converts the IL-13Ralpha1b into a receptor that can only signal via IL-4 ligation. The existence of duplicated receptor genes perhaps suggests that more ligands still remain to be discovered that will bind these receptors. The duplicated receptors are differentially expressed in most tissues and cell lines examined, and their expression can be modulated by LPS, polyIC and IFN-gamma in cell lines. In contrast, the T-cell stimulant phytohaemagglutinin increased the expression of IL-4Ralpha1 and IL-4Ralpha2, but not IL-13Ralpha1/2, suggesting a role of an IL-4-like molecule in T-cell growth/activation in fish.