Immune regulation the cytokine network in fish

1 The cytokines and transcription factors involved in mammalian Th cell development 

The IL-12 family cytokines (IL-12, IL-23, IL-27 and IL-35) are heterodimers, with IL-12 and IL-23 important growth factors for Thl and Thl7 cells respectively, whilst IL-27 has broad inhibitory effects on all effector Th subsets whilst expanding inducible Tregs (Yoshida et al., 2009 Jankowski et al, 2010). In contrast IL-35 is produced by Tregs and serves to suppress inflammatory responses but induces Treg proliferation (Castellani et al., 2010). The peptide chains that form these interleukins include pl9, p28, p35, p40 and Epstein-Barr virus induced gene 3 (EBB). Thus, IL-12 is composed of p35 and p40, IL-23 of pl9 and p40, IL-27 of p28 and EBB and IL-35 of p35 and EBB. In addition it is known that the p40 homodimer is 

Lastly, IL-22 is a cytokine released by Th-17 cells in mammals and crucial for protection against extracellular microbes and at mucosal sites (Kolls, 2010). IL-22 has been cloned in several fish species but only trout IL-22 has been produced as a bioactive recombinant protein. Trout rIL-22 expression is induced in the spleen upon infection of fish with the Gram-negative 

Helios is also conserved in fish (John et al., 2009), and thus conservation of Tregs and their functions in early vertebrates seems likely. 

Human and mouse CD4 T cells can also develop into a variety of Treg cell populations defined by expression of the transcription factor FoxP3 and by their capacity to produce cytokines such as TGF-P and IL-10. FoxP3, TGF-P and lL-10 are present in the genomes of several fish species, although none of them have yet been associated with a defined Treg cell subset. 

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