The expanding repertoire of the IL-12 cytokine family in teleost fish: Identification of three paralogues each of the p35 and p40 genes in salmonids, and comparative analysis of their expression and modulation in Atlantic salmon Salmo salar

• Four salmonid p35 loci are discovered for three active p35 and a p35 pseudogene.
• Multiple p35 genes in fish were originated from whole genome duplications.
• Multiple p35 and p40 paralogues expand the repertoire of IL-12, IL-23 and IL-35 in fish.
• Paralogues of p35 and p40 are differentially expressed and modulated by PAMPs and cytokines.
• The expanded IL-12 family hints at a complex network to fine tune the immune response in fish.

Interleukin (IL)-12 family cytokines are heterodimers of an α-chain (p19, p28 and p35) and a β-chain (p40 and Ebi3), present as IL-12 (p35/p40), IL-23 (p19/p40), IL-27 (p28/Ebi3) and IL-35 (p35/Ebi3), and play key roles in immune responses in mammals. One p35 and up to three p40 genes have been cloned in some fish species. The identification of three active p35 genes, along with three p40 paralogues in salmonids in the current study further expands the repertoire of IL-12, IL-23 and IL-35 molecules in these species. The multiple p35 genes in teleost fish appear to have arisen via whole genome duplications. The different paralogues of the subunits are divergent, and differentially expressed and modulated by PAMPs and proinflammatory cytokines, hinting that distinct isoforms could be produced in response to infection. Therefore, the expanded IL-12 cytokine family may provide an unprecedented level of regulation to fine tune the immune response in fish.