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

Healthy fish stocks are central to global food security. Key to fish health is robust immunity at mucosal surfaces, and especially at the gills. However, a balance must be struck between tolerating commensal microorganisms and reacting appropriately toward pathogens. In mammals, IL-4 and IL-13 in concert with IL-10 are essential for balancing immune response to pathogens and suppressing inflammation. Whether their fish counterparts perform similar roles is an open question. Here, we have generated IL-4/13A and IL-4/13B mutant zebrafish and, together with existing IL-10 mutants, characterized the consequences of loss-of-function of these cytokines. We demonstrate that these cytokines are required to suppress inflammation. Further, IL-4/13A and IL-4/13B are required for the maintenance of a Th2-like phenotype in the gills. As in mammals, IL-10 appears to have a more striking anti-inflammatory function than IL-4-like cytokines. Thus, both IL-10 and IL-4/13 paralogues in zebrafish exhibit aspects of conserved function with their mammalian counterparts. ### Competing Interest Statement The authors have declared no competing interest.