title: IL-22 is a key player in the regulation of inflammation in fish and involves innate immune cells and PI3K signaling.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Marinas (IIM), CSIC, Eduardo Cabello 6, 36208 Vigo, Spain. Electronic address: marimarcp@iim.csic.es.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Costa
authors.forename: Paolo R
authors.initials: PR
authors.lastname: Saraceni
authors.forename: Gabriel
authors.initials: G
authors.lastname: Forn-Cuní
authors.forename: Sonia
authors.initials: S
authors.lastname: Dios
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueras
authors.forename: Beatriz
authors.initials: B
authors.lastname: Novoa
mesh_terms: D016980:Aeromonas hydrophila / Q000276:immunology; D048409:Aeromonas salmonicida / Q000276:immunology; D000818:Animals; D005393:Fish Diseases / Q000276:immunology; D005399:Fishes; D005412:Flatfishes / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction; D015027:Zebrafish / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D019869:Phosphatidylinositol 3-Kinases; D011994:Recombinant Proteins; D000097043:Interleukin-22
keywords: Aeromonas; IL-22; Inflammation; PI3K; Turbot; Zebrafish