期刊
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
卷 41, 期 4, 页码 746-755出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2013.08.021
关键词
IL-22; Inflammation; Zebrafish; Turbot; PI3K; Aeromonas
资金
- AQUAGENOMICS of the program Consolider-Ingenio, Spanish Ministerio de Ciencia e Innovacion (MICINN) [CSD2007-00002]
- FISH-FORPHARMA (EU) [289209]
- Proyecto Intramural Especial, PIE, Agencia Estatal Consejo Superior de Investigaciones Cientificas (CSIC) [201230E057]
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. (C) 2013 Elsevier Ltd. All rights reserved.
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