Bbe-miR-210 modulates AP-1-driven innate immune responses to LPS in amphioxus via targeting AmphiFos and AmphiJun

Abstract

The activator protein 1 (AP-1) family, a group of dimerized transcription factors ubiquitously expressed in mammalian cells, plays versatile roles in diverse cellular and physiological processes. However, the functional characteristics of AP-1 remains unexplored in amphioxus (Branchiostoma belcheri tsingtauense), an evolutionarily pivotal chordate model for studying the origins of vertebrate development and immunity. Here, we report the discovery and functional characterization of two novel AP-1 subunit homologs, designated as AmphiFos and AmphiJun, in amphioxus. Our findings demonstrate that both AmphiFos and AmphiJun are involved in the innate immune response to lipopolysaccharide (LPS) challenge. Furthermore, the AmphiFos/AmphiJun heterodimer binds specifically to the conserved AP-1 DNA motif and activates downstream cytokine expression. Intriguingly, we have identified bbe-miR-210 as a post-transcriptional regulator that directly targets the coding sequences of both AmphiFos and AmphiJun, thereby suppressing their expressions to balance immune responses. Collectively, this work not only reveals the evolutionary conservation of AP-1-mediated immune regulation in basal chordates but also uncovers a mechanism by which microRNA fine-tunes AP-1 activity in amphioxus.