In mammals, IL-22 has been reported to have a role in different disorders including mucosal associated infections and inflammatory diseases. However, no functional studies have been reported to date for any non-mammalian IL-22. In this work, recombinant IL-22 (rIL-22) from turbot (Scophthalmus maximus) has been produced to investigate its effects as a bioactive molecule. The expression of several pro-inflammatory cytokines was increased after rIL-22 treatment, which was reduced when a previous treatment with the specific JAK/STAT and PI3K pathway inhibitors, Stattic V and Wortmannin, was conducted. The involvement of the PI3K pathway was also demonstrated using the mutant zebrafish (Danio rerio) line pten - /- . rIL-22 was able to reduce the mortality in Aeromonas salmonicida infected turbot, while a higher mortality was observed after an Aeromonas hydrophila or LPS stimulation when IL-22 expression was blocked with morpholinos using a whole animal zebrafish model. The IL-22 knockdown induced also an increment of the pro-inflammatory cytokines expression in bacteria stimulated fish but not under control conditions. In zebrafish, IL-22 expression was detected in innate cells, since it was found in the earliest developed stages when the adaptive immune response is not yet functional or in rag1 - /- fish that lack the adaptive immune system. Our results clarify the conserved and important role of IL-22 in lower vertebrates for the first time suggesting that it constitutes a key regulator on the inflammatory balance homeostasis even in distant species such as teleosts, which diverged from mammals more than 350 million years ago

First International Conference of Fish and Shellfish Immunology (ISFSI), Vigo (España), 25-28 June 2013

Peer reviewed