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

The mammalian gamma-chain (gamma C) 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 gamma C and a private alpha chain, and in the case of IL-2 and IL-15 an additional common IL-2/15R beta chain. Deficiency of gamma C signalling in mammals prevents CD4(+) T cells from developing effector functions and CD8(+) T cells from developing immunological memory. Thus gamma C cytokines are critical for the generation and peripheral homeostasis of naive and memory T cells. This review will give an update on the gamma C ligands and receptor subunits in fish, and also present some new data on the cloning and expression of a second gamma C and two IL-2R beta 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 gamma C 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 rainbow trout, including gamma C itself, IL-2R beta, IL-4R alpha., IL-13R alpha 1, IL-13R alpha 2 and IL-2/15R alpha, 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 gamma C cytolcines is beginning but made more difficult by the co-existence of so many paralogues of the ligands and their receptors. Initial functional studies have shown that fish gamma C cytokines can modulate the expression of key cytokines (e.g. interferon-gamma, IL-10 and IL-22) of the adaptive immune response, and may thus have promise as adjuvants to improve vaccination efficiency in fish. (C) 2011 Elsevier Ltd. All rights reserved.