ZFIN ID: ZDB-PUB-171220-5
Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs
Hui, S.P., Sheng, D.Z., Sugimoto, K., Gonzalez-Rajal, A., Nakagawa, S., Hesselson, D., Kikuchi, K.
Date: 2017
Source: Developmental Cell   43: 659-672.e5 (Journal)
Registered Authors: Hesselson, Daniel, Hui, Subhra Prakash, Kikuchi, Kazu, Sheng, Delicia
Keywords: cardiomyocyte, heart, neural stem cell, regeneration, regulatory T cell, retina, spinal cord, zebrafish
MeSH Terms:
  • Animals
  • Cell Differentiation/physiology
  • Cell Proliferation/physiology
  • Forkhead Transcription Factors/physiology
  • Heart/physiology
  • Models, Animal
  • Nerve Regeneration/physiology
  • Organogenesis/immunology
  • Organogenesis/physiology
  • Regeneration/physiology*
  • Retina/physiology
  • Spinal Cord/physiology
  • T-Lymphocytes, Regulatory/physiology*
  • Zebrafish/physiology*
  • Zebrafish Proteins/physiology
PubMed: 29257949 Full text @ Dev. Cell
The attenuation of ancestral pro-regenerative pathways may explain why humans do not efficiently regenerate damaged organs. Vertebrate lineages that exhibit robust regeneration, including the teleost zebrafish, provide insights into the maintenance of adult regenerative capacity. Using established models of spinal cord, heart, and retina regeneration, we discovered that zebrafish Treg-like (zTreg) cells rapidly homed to damaged organs. Conditional ablation of zTreg cells blocked organ regeneration by impairing precursor cell proliferation. In addition to modulating inflammation, infiltrating zTreg cells stimulated regeneration through interleukin-10-independent secretion of organ-specific regenerative factors (Ntf3: spinal cord; Nrg1: heart; Igf1: retina). Recombinant regeneration factors rescued the regeneration defects associated with zTreg cell depletion, whereas Foxp3a-deficient zTreg cells infiltrated damaged organs but failed to express regenerative factors. Our data delineate organ-specific roles for Treg cells in maintaining pro-regenerative capacity that could potentially be harnessed for diverse regenerative therapies.