Transcription factor Rel regulates the transcription of effector genes involved in immune response by cooperating with IκBs in lamprey (Lethenteron reissneri).

The Rels, a class of nuclear factor κB (NF-κB) complexes, regulate diverse physiological processes by modulating the transcription of effector genes. IκBs are the critical proteins that inhibit NF-κB nuclear translocation, thereby disrupting NF-κB-mediated signaling pathways. Despite this, the precise role and underlying molecular mechanisms of Rel and IκB transcriptional regulation mediated in lamprey, a member of the oldest surviving vertebrates, remain incompletely understood. In this study, we cloned and identified 4 Rels (designated Lr_Rels) and IκBs (designated Lr_IκBs) from lamprey and explored their sequence structures and evolutionary process, indicating that Lr_Rels and Lr_IκBs represent ancestral lineages in vertebrates, and the dimerization domain (DD) might be crucial for Lr_Rels' function. Immunoreactivity assays demonstrated a significant induction of Lr_Rel1 expression across various lamprey tissues following LPS and polyinosinic-polycytidylic acid (poly (I:C)) challenge. Functional characterization revealed that Lr_Rel1 mediates the NF-κB signaling through nuclear translocation and sequence-specific recognition, with its activity being inhibited by Lr_IκBs. Furthermore, the Rel homology region (RHR) and transcriptional activation domain (TAD) were identified as key elements for Lr_Rel1 function. Thirteen target genes of Lr_Rel1 were also identified, each containing conserved κB-binding sites within their promoter regions. Our study revealed the cooperation between Lr_Rel and Lr_IκBs, providing insights into the molecular mechanisms of lamprey Rel protein in the immune regulation signaling pathway.