Japanese eel SOCS1 suppresses MyD88-mediated NF-κB activation: implications for negative regulation of innate immunity in teleosts.

Suppressor of cytokine signaling 1 (SOCS1) is a pivotal negative regulator of cytokine-mediated signaling in mammals, yet its role in teleost fish immunity remains poorly understood. In this study, we cloned and characterized the full-length SOCS1 cDNA from Japanese eel (Anguilla japonica), which encodes a 203-amino acid protein containing a conserved SH2 domain and SOCS box. Phylogenetic analysis placed AjSOCS1 within the teleost clade, showing high conservation with other vertebrate SOCS1 homologs. AjSOCS1 was ubiquitously expressed across tissues, with the highest levels in intestine and immune-related organs. Its transcription was significantly induced both in vivo (lipopolysaccharide [LPS], polyinosinic-polycytidylic acid [poly(I:C)], Aeromonas hydrophila) and in vitro (pathogen-associated molecular patterns [PAMPs] and bacterial infection), highlighting responsiveness to bacterial and viral stimuli. Subcellular localization analysis demonstrated that AjSOCS1 is cytoplasmic, consistent with its role in intracellular signaling regulation. Functional assays using a dual-luciferase reporter system revealed that AjSOCS1 strongly suppressed NF-κB activation under basal conditions, as well as during MyD88-, LPS-, and poly(I:C)-induced stimulation, and overexpression of AjSOCS1 resulted in coordinated downregulation of NF-κB subunits and downstream inflammatory and antimicrobial genes. Together, these findings provide the first functional evidence that SOCS1 in Japanese eel acts as a negative regulator of NF-κB signaling, thereby extending the known repertoire of SOCS1 activity in fish. This study not only enriches comparative immunology of SOCS proteins but also has potential implications for controlling excessive inflammation and improving disease resistance in aquaculture.