The gamma-chain cytokine/receptor system in fish: More ligands and receptors

Abstract

Themammalian gamma-chain (gC) cytokine family consists of interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21. They signal through a receptor complex containing the common gC and a private alpha chain, and in the case of IL-2 and IL-15 an additional common IL-2/15Rb chain. Deficiency of gC signalling inmammals prevents CD4þ T cells from developing effector functions and CD8þ T cells from developing immunological memory. Thus gC cytokines are critical for the generation and peripheral homeostasis of naïve and memory T cells. This review will give an update on the gC ligands and receptor subunits in fish, and also present some new data on the cloning and expression of a second gC and two IL-2Rb chains in rainbow trout Oncorhynchus mykiss. In recent years, aided by the availability of sequenced fish genomes and expressed sequence tag databases, five of the six mammalian gC cytokines and their cognate receptors have been discovered in fish, with only the IL-9/IL-9R homologues apparently absent. Paralogues have been discovered in diploid fish and all the receptors described in the tetraploid rainbowtrout, including gC itself, IL-2Rb, IL-4Ra, IL-13Ra1, IL-13Ra2 and IL-2/15Ra, have duplicates. As a consequence of the teleost and salmonid whole genome duplications, even more paralogues may yet be discovered. Some of the paralogues have changes in domain structures and show differential expression and modulation, suggesting the potential for a change in function. Functional characterisation of fish gC cytokines is beginning butmademore difficult by the co-existence of somany paralogues of the ligands and their receptors. Initial functional studies have shown that fish gC cytokines can modulate the expression of key cytokines (e.g. interferon-g, IL-10 and IL-22) of the adaptive immune response, andmay thus have promise as adjuvants to improve vaccination efficiency in fish.