Akirin2 regulates IL-6 expression and contributes to immune defense in silver pomfret (Pampus argenteus)

Akirin2 is a highly conserved nuclear factor that regulates immune factor expression and has been associated with NF-κB activity in innate immune responses. The silver pomfret (Pampus argenteus), a commercial important marine fish, is susceptible to pathogens such as Cryptocaryon irritans, which causes white spot disease and immune-related tissue damage. In the present study, P. argenteus Akirin2 (PaAkirin2) was cloned from the head kidney and its function was characterized by RNA interference (RNAi) and overexpression in P. argenteus liver (PaL) cells. PaAkirin2 contained conserved nuclear localization signals and exhibited high homology with Akirin2 from related species. To assess its potential immune role, we analyzed its functional relationship with NF-κB-associated immune components including PaIL-6 and PaMyD88. LPS stimulation induced an early response of PaAkirin2 and PaIL-6 in immune tissues, with delayed induction of PaMyD88 observed in the liver. Functional studies in PaL cells demonstrated that PaAkirin2 overexpression activated NF-κB signaling, whereas its knockdown suppressed both NF-κB and PaIL-6 expression. Dual-luciferase assays confirmed that overexpression of either PaAkirin2 or PaMyD88 enhanced NF-κB-driven transcription and promoted IL-6 expression. Mutagenesis analysis identified AP-1 and NF-κB binding sites as essential for LPS-induced PaIL-6 transcription. Collectively, PaAkirin2 functions as a nuclear immunoregulator influencing NF-κB activity, directing immune defenses via transcriptional control of PaIL-6 and synergistic coordination with PaMyD88. This work provides the first mechanistic framework for Akirin2-mediated immunoregulation in teleosts, offering valuable insights for aquaculture disease management.