Japanese flounder Paralichthys olivaceus interleukin 21 induces inflammatory response and plays a vital role in the immune defense against bacterial pathogen

Interleukin (IL)-21 is a pleiotropic cytokine and plays a vital role in immunity. In the current study, we examined the immune function of Japanese flounder Paralichthys olivaceus IL-21 (PoIL-21). PoIL-21 shares moderate (25.17%-46.25%) sequence identities with other teleost IL-21. PoIL-21 expression occurred in multiple tissues, especially intestine, and was regulated by bacterial infection in a time dependent manner. PoIL-21 was secreted by peripheral blood leukocytes (PBL) upon LPS stimulation. Recombinant PoIL-21 (rPoIL-21) bound to a wide range of Gram-negative and Gram-positive bacteria and inhibited the growth of the fish bacterial pathogen Streptococcus iniae. rPoIL-21 also interacted with PBL, resulting in enhanced cell proliferation, ROS production, and expression of IL-1 beta, TNF-alpha, CD8 beta, T-bet, PoIL-21, PoIL-21 receptor, and STAT. Consequently, the presence of rPoIL-21 significantly reduced bacterial infection in PBL. In vivo study showed that rPoIL-21 upregulated the expression of inflammatory cytokines and PoIL-21. Taken together, these results indicate that PoIL-21 is an inducible, secreted cytokine with a broad range of binding capacities and plays an important role in the regulation of anti-bacterial immunity.