Trawling the depths of gene regulation: transcription–factor families orchestrating immunity in teleost fish

Abstract

Transcription factors act as central regulators of immune responses by integrating signals from immunological pathways and translating them into cell type-specific gene-expression programmes. Dynamic networks of transcription factors and co-factors control the activation, polarisation and functional specialisation of immune cells, thereby coordinating the magnitude, timing and specificity of responses to pathogenic stimuli whilst promoting the restoration of homeostasis. Although immune-relevant transcription factors have been extensively studied in mammals, the molecular principles governing transcriptional initiation and regulation by transcription factor networks remain incompletely understood across vertebrates. This knowledge gap is particularly evident in teleost fish, which possess unique anatomical and genomic features, including lineage-specific gene duplications that have shaped immune regulatory networks. Moreover, teleosts have evolved or expanded immune-cell functions that may involve novel combinations of conserved transcription factors, potentially giving rise to regulatory modules distinct from those characterised in mammals. It remains unclear how defined immunological stimuli are translated into stimulus-specific transcriptional programmes through the coordinated action of signalling pathways, transcription factors and chromatin-associated regulatory mechanisms. This review focuses on the transcriptional regulation of immune responses in teleost fish and provides an overview of immune-relevant transcription factors involved in immediate-early and delayed primary responses, as well as secondary and lineage-specific transcriptional programmes in representative model–fish species. By integrating current knowledge from teleost models, this review aims to establish a framework for understanding immune transcriptional regulation in fish, highlight conserved and lineage-specific regulatory mechanisms and identify key challenges for future research in non-mammalian vertebrate immunology.