Identification and expression analysis of IL-4/13 receptors in grass carp Ctenopharyngodon idella

Interleukin (IL)-4 and IL-13 are T helper 2 (Th2) cytokines with pleiotropic functions. IL-4 interacts with two receptors consisting of IL-4R alpha/gamma chain receptor (gamma C) and IL-4R alpha/IL-13R alpha 1. In contrast, IL-13 binds to IL-13R alpha 2 but also shares the receptor complex containing IL-4R alpha/IL-13R alpha 1. In fish, two IL-4/13 homologs have been identified but their phylogenetic relationships with IL-4 and IL-13 are ambiguous. In this study, we identified six putative IL-4/13 receptor homologs in grass carp, including gamma Ci, gamma C2, IL-4R alpha 1, IL-13R alpha 1, IL-13R alpha 2 and a soluble form of IL-4R alpha 2. Comparative sequence analyses revealed that these receptors possess conserved characteristic domains and the genes encoding them share conserved gene synteny with their human counterparts. All six receptors contain a cytokine binding homology domain (CHD) and two fibronectin type III (FNIII) like domains, with IL-13R alpha 1 and IL-13R alpha 2 harbouring an extra Ig-like domain preceding the CHD domain. Interestingly, grass carp IL-13R alpha 1 and IL-13R alpha 2 lack the characteristic WSXWS motif, a typical feature of mammalian type I cytokine receptors. The IL-4/13 receptor genes are differentially expressed in tissues and primary leukocytes of head kidney and can be modulated by Fiavobacterium cloumnare (F. clownnare), suggesting they are involved in immune response against F. cloumnare infection