Fish Meteorin-like factor promotes migration, proliferation and phagocytic activity of monocytes/macrophages

Meteorin-like (Metrnl) is a cytokine known to play multifunctional roles in mammalian immunity, yet its immunoregulatory role in teleost remains largely unexplored. In the present study, we systematically investigate the effects of Metrnl on primary monocytes/macrophages (Mo/Mφ) in grass carp (Ctenopharyngodon idella). In vitro, Metrnl significantly increased the viability of primary Mo/Mφ, with increases of 12.7% on day 3 and 7.9% on day 6, as determined by flow cytometric quantification of MCSFR⁺ cells across multiple biological replicates. Furthermore, Metrnl stimulation promoted Mo/Mφ proliferation and phagocytic activity, resulting in absolute increases of 12.43% and 16.86%, respectively, calculated as the proportion of EdU⁺MCSFR⁺ or Beads⁺MCSFR⁺ cells within the total MCSFR⁺ population. Consistent with these findings, in vivo experiments using a Metrnl-expressing plasmid demonstrated enhanced Mo/Mφ proliferation and phagocytosis. Moreover, Metrnl also significantly upregulated the mRNA levels of the chemokines Cxcl8 and Cxcl11.1b, indicating its ability to recruit Mo/Mφ to target sites by activating chemokine-mediated chemotactic signaling. Importantly, neutralization of Metrnl with a specific antibody markedly impaired the enhanced Mo/Mφ recruitment, proliferation and phagocytosis, confirming that the effect is specifically mediated by Metrnl. Our results demonstrate that Metrnl acts as an important regulatory factor that activates and enhances Mo/Mφ-mediated innate immune response.