Swimming Through Dendritic Cell Biology: Insights From Fish Models

Dendritic cells (DCs) are central to vertebrate immunity, bridging innate and adaptive responses. While DC biology has been extensively studied in mammals, how this cell population is evolutionarily developed and adapted to the ancient immune system of the non-mammalian vertebrates remains poorly understood. Fish, the earliest vertebrates with a fully developed adaptive immune system, offer unique opportunities to explore the evolutionary emergence and diversification of DCs. Early studies in fish, relying on conserved phenotypical markers and morphological observations, hinted at the existence of DC-like populations but lacked definitive validation. Recent advances in single-cell transcriptomics, combined with powerful genetic resources in model organisms like zebrafish, enable the precise identification and characterization of these cells. In this review, we summarize the historical and current understanding of DCs in fish, with a particular focus on zebrafish studies. We highlight both conserved and species-specific features of their development and function, and further elaborate on two special DC populations that are unique to fish. By integrating evolutionary immunology with cutting-edge technologies, zebrafish DC research is poised to provide fundamental insights into antigen-presenting cell biology.