Recombinant IL-21 alleviates bacterial enteritis in grass carp by enhancing the intestinal barrier and suppressing the inflammatory response.

Abstract

Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates immune responses, but its role in fish intestinal immunity remains poorly understood. In this study, we produced recombinant grass carp IL-21 (rCiIL-21) and investigated its protective effects against Aeromonas hydrophila-induced enteritis. Administration of rCiIL-21 significantly reduced intestinal bacterial load and mitigated histopathological damage caused by A. hydrophila infection. Furthermore, rCiIL-21 treatment enhanced intestinal barrier integrity by increasing mucus layer thickness, promoting goblet cell proliferation, and upregulating the expression of mucin-related genes (agr2, muc2, and klf4) and tight junction proteins (zo-1, claudin-3, and occludin) after infection. Additionally, rCiIL-21 attenuated apoptosis and oxidative stress while promoting the expression of antimicrobial factors (c-lysozyme, β-defensin 1 and β-defensin 2) and anti-inflammatory factor (il-10), collectively leading to reduced bacterial load and improved survival rates. Collectively, these results demonstrate that rCiIL-21 plays a multiple role in alleviating bacterial enteritis by reinforcing intestinal barrier integrity, modulating inflammatory responses, and enhancing innate antimicrobial defense, highlighting its potential as a therapeutic agent for bacterial enteritis in aquaculture.