Zebrafish IL-4-like cytokines and IL-10 suppress inflammation but only IL-10 is essential for gill homeostasis

Mucosal surfaces such as fish gills interface between the organism and the external environment and as such are major sites of foreign Ag encounter. In the gills, the balance between inflammatory responses to waterborne pathogens and regulatory responses toward commensal microbes is critical for eff...

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Bibliographic Details
Published in:The Journal of Immunology
Main Authors: Bottiglione, F, Dee, CT, Lea, R, Zeef, LAH, Badrock, AP, Wane, M, Bugeon, L, Dallman, MJ, Allen, JE, Hurlstone, AFL
Format: Article in Journal/Newspaper
Language:English
Published: American Association of Immunologists 2020
Subjects:
Science & Technology
Life Sciences & Biomedicine
Immunology
TROUT ONCORHYNCHUS-MYKISS
SALMO-SALAR-L
SET ENRICHMENT ANALYSIS
ATLANTIC SALMON
TYPE-2 IMMUNITY
T-CELLS
EXPRESSION ANALYSIS
ADAPTIVE IMMUNITY
LYMPHOID-TISSUE
HEAD KIDNEY
1107 Immunology
Atlantic salmon
Salmo salar
Online Access:http://hdl.handle.net/10044/1/83214
https://doi.org/10.4049/jimmunol.2000372
Description
Summary:Mucosal surfaces such as fish gills interface between the organism and the external environment and as such are major sites of foreign Ag encounter. In the gills, the balance between inflammatory responses to waterborne pathogens and regulatory responses toward commensal microbes is critical for effective barrier function and overall fish health. In mammals, IL-4 and IL-13 in concert with IL-10 are essential for balancing immune responses to pathogens and suppressing inflammation. Although considerable progress has been made in the field of fish immunology in recent years, whether the fish counterparts of these key mammalian cytokines perform similar roles is still an open question. In this study, we have generated IL-4/13A and IL-4/13B mutant zebrafish (Danio rerio) and, together with an existing IL-10 mutant line, characterized the consequences of loss of function of these cytokines. We demonstrate that IL-4/13A and IL-4/13B are required for the maintenance of a Th2-like phenotype in the gills and the suppression of type 1 immune responses. As in mammals, IL-10 appears to have a more striking anti-inflammatory function than IL-4–like cytokines and is essential for gill homeostasis. Thus, both IL-4/13 and IL-10 paralogs in zebrafish exhibit aspects of conserved function with their mammalian counterparts.

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