IL-22 is a key player in the regulation of inflammation in fish and involves innate immune cells and PI3K signaling

• Published in: Developmental & Comparative Immunology
• Main Authors: Costa, M. M., Saraceni, Paolo R., Forn-Cuni, Gabriel, Dios, S., Romero Jódar, Alejandro, Figueras Huerta, Antonio, Novoa, Beatriz
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2013
• Subjects: IL-22; Inflammation; Zebrafish; Turbot; PI3K; Aeromonas
• Online Access: http://hdl.handle.net/10261/83509; https://doi.org/10.1016/j.dci.2013.08.021

10 páginas, 5 figuras, 1 tabla IL-22 plays a role in various disorders in mammals, including mucosal-associated infections and inflammatory diseases. No functional IL-22 studies have been conducted on non-mammals to date. In this study, recombinant IL-22 (rIL-22) from turbot was produced to investigate its effects as a bioactive molecule. The expression of several pro-inflammatory cytokines was increased after rIL-22 treatment and reduced by pre-treatment with a JAK/STAT inhibitor. The involvement of the PI3K pathway in IL-22 induction was demonstrated. rIL-22 reduced the mortality in Aeromonas salmonicida-infected turbot, while higher Aeromonas hydrophila- or LPS-induced mortality was observed when IL-22 was blocked in zebrafish embryos. IL-22 knockdown increased pro-inflammatory cytokine expression in bacteria-stimulated fish. In zebrafish, IL-22 expression was detected primarily in the myeloid innate linage. It was found during early developmental stages when the adaptive immune response is not yet functional and in rag1−/− fish that lack an adaptive immune system. Our results clarify the conserved role of IL-22 in lower vertebrates. We suggest for the first time that IL-22 constitutes a key regulator of inflammatory homeostasis even in distant species such as teleosts, which diverged from mammals more than 350 million years ago. This work was supported by the projects CSD2007-00002 ‘‘AQUAGENOMICS’’ of the program Consolider-Ingenio 2010, Span- ish Ministerio de Ciencia e Innovación (MICINN); 289209 ‘‘FISH- FORPHARMA’’ (EU) and 201230E057 ‘‘Proyecto Intramural Especial, PIE’’, Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC). Peer reviewed