Identification and characterization of T reg-like cells in zebrafish

J Exp Med. 2017 Dec 4;214(12):3519-3530. doi: 10.1084/jem.20162084. Epub 2017 Oct 24.


Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg-like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.

MeSH terms

  • Animals
  • Base Sequence
  • Chronic Disease
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / metabolism
  • Hematopoiesis
  • Inflammation / pathology
  • Lymphocytes / metabolism
  • Mutation / genetics
  • Phylogeny
  • Splenomegaly / pathology
  • Survival Analysis
  • T-Lymphocytes, Regulatory / immunology*
  • Thymocytes / metabolism
  • Zebrafish / genetics
  • Zebrafish / immunology*
  • Zebrafish Proteins / deficiency
  • Zebrafish Proteins / metabolism


  • Zebrafish Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins

Associated data

  • RefSeq/NP_001316496
  • RefSeq/XM_021478427
  • RefSeq/NP_001231745
  • RefSeq/NP_055306
  • RefSeq/NP_001012426
  • RefSeq/NP_001186277
  • RefSeq/NP_001121199
  • GENBANK/ABQ15210
  • GENBANK/ADD91631