IL-22 is a key player in the regulation of inflammation in fish and involves innate immune cells and PI3K signaling
- Authors
- Costa, M.M., Saraceni, P.R., Forn-Cuní, G., Dios, S., Romero, A., Figueras, A., and Novoa, B.
- ID
- ZDB-PUB-130905-25
- Date
- 2013
- Source
- Developmental and comparative immunology 41(4): 746-755 (Journal)
- Registered Authors
- Figueras, Antonio, Novoa, Beatriz
- Keywords
- IL-22, inflammation, zebrafish, turbot, PI3K, Aeromonas
- MeSH Terms
-
- Aeromonas hydrophila/immunology
- Aeromonas salmonicida/immunology
- Animals
- Fish Diseases/immunology
- Fishes
- Flatfishes/immunology
- Immunity, Innate/immunology*
- Inflammation/immunology*
- Interleukins/immunology*
- Phosphatidylinositol 3-Kinases/immunology*
- Recombinant Proteins/immunology
- Signal Transduction
- Zebrafish/immunology
- PubMed
- 23999050 Full text @ Dev. Comp. Immunol.
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 A. 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.