New function of zebrafish regulatory T cells in organ regeneration

Abstract

Zebrafish can efficiently regenerate complex tissue structures with a highly developed innate and adaptive immune system, which provides a model to investigate the roles of immune cells in tissue repair and regeneration. Two groups recently reported zebrafish mutants deficient in a forkhead box P3 (FOXP3) ortholog, which helped reveal the conserved immunosuppressive function of zebrafish FOXP3 in vivo. Zebrafish FOXP3 defines the development of a subset of T cell lineage with the conserved gene expression profile of mammalian regulatory T cells (Tregs). In damaged organs, zebrafish Tregs rapidly migrate to the injury site, where they promote the proliferation of regeneration precursor cells by producing tissue-specific regenerative factors through a distinct mechanism from the canonical anti-inflammatory pathway. These findings illuminate the potential for using zebrafish as an effective model in Treg research and demonstrate organ-specific roles for Tregs in maintaining proregenerative capacity that could potentially be harnessed for use in diverse regeneration therapies.