Exploring the immunological functions of thioredoxin domain-containing protein 17 (TXNDC17) in chub mackerel (Scomber japonicus): Immune response and cellular redox homeostasis

All organisms have evolved sophisticated antioxidant networks and enzymes to counteract reactive radicals, among which thioredoxin (Trx) systems are especially noteworthy. Thioredoxin domain-containing protein 17 (TXNDC17) is a ubiquitously expressed enzyme with oxidoreductase activity belonging to the Trx protein family. This study successfully uncovered and analyzed the TXNDC17 gene in Scomber japonicus (SjTXNDC17). The gene consists of a 372-base-pair coding sequence that encodes a protein of 123 amino acids, with an estimated molecular weight of 14.1 kDa. Structural analysis revealed that SjTXNDC17 contains a TRX-related protein 14 domain with two redox-responsive cysteine residues in the 42WCPDC46 motif. Spatial expression analysis indicated that SjTXNDC17 had the highest constitutive expression in the brain. Stimulation with polyinosinic-polycytidylic acid (poly I:C), Vibrio harveyi, and Streptococcus iniae, significantly upregulated the mRNA levels of SjTXNDC17 in the head kidney. The antioxidant activity of the recombinant SjTXNDC17 protein was evidenced by 2,2-Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging, insulin reduction, and cupric ion-reducing antioxidant capacity assays. SjTXNDC17 overexpression in fathead minnow (FHM) cells significantly reduced reactive oxygen species (ROS) levels and decreased apoptosis. The anti-apoptotic effect was driven by the upregulation of the Bcl2 gene and the downregulation of the Bax gene, as well as the suppression of JNK signaling pathway genes. Moreover, overexpression of SjTXNDC17 facilitated M2 polarization and suppressed nitric oxide production in macrophages. Collectively, these results demonstrate that SjTXNDC17 plays a crucial role in both the immune response and cellular redox balance in Scomber japonicus. •Thioredoxin domain-containing protein 17 (SjTXNDC17) was identified in chub mackerel.•Pathogen stimulation significantly increased SjTXNDC17 mRNA levels in head kidney.•The recombinant SjTXNDC17 protein showed antioxidant activity.•Overexpression of SjTXNDC17 reduced ROS levels and apoptosis in FHM cells.•SjTXNDC17 overexpression promoted M2 polarization and lowered NO production.