Neuroimmune regulation of inflammation: RNA-Seq study of somatostatin-6 effects in gilthead seabream (Sparus aurata) skin and brain

This study evaluated the anti-inflammatory potential of gilthead seabream somatostatin-6 (SST6) in a λ-carrageenan-induced inflammation model using RNA-seq transcriptomics. We compared gene expression in the skin (primary site of sterile inflammation) and brain (main neuropeptide reservoir) to determine if peripheral signaling elicits coordinated local and central reprogramming, indicative of a neuroimmune axis during inflammation. The results showed that λ-carrageenan induced significant transcriptomic changes, particularly in the skin, while SST6 exerted a more substantial modulatory effect in the brain. Functional enrichment analysis revealed distinct pathway variations across conditions, with λ-carrageenan activating general metabolism, apoptosis, and proteasome degradation in the skin, while repressing innate immune response and neurogenesis. In the brain, λ-carrageenan activated NF-κB cascade, neurotransmitter release, and apoptotic mechanisms, while repressing neuronal development and PTEN regulation. SST6 treatment sustained the activation of adaptive immunity and neural pathways in the skin, while activating RNA-synthesis regulation, sensory-organ development, and neurotransmitter transport/release in the brain. The combined treatment (λ-carrageenan + SST6) showed a reversal of some λ-carrageenan-induced changes, particularly in the brain. This study provides novel insights into the anti-inflammatory action of a cortistatin functional analogue in teleosts, paving the way for strategies to bolster fish welfare and resilience under inflammatory challenges. • λ-carrageenan induced significant transcriptomic changes, particularly in the skin.SST6 exerted a more substantial modulatory effect in the brain. • λ-carrageenan activated metabolism, apoptosis, and proteasome degradation in the skin. • λ-carrageenan repressed innate immunity and neurogenesis in the skin. • In the brain,λ-carrageenan activated NF-κB, neurotransmitter release, and apoptotic mechanisms. • SST6 treatment sustained adaptive immunity and neural pathways in the skin. • SST6 activated RNA-synthesis, sensory-organ development, and neurotransmitter transport/release in the brain.