Developmental Cell
Volume 43, Issue 6, 18 December 2017, Pages 659-672.e5
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Article
Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs

https://doi.org/10.1016/j.devcel.2017.11.010Get rights and content
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Highlights

  • Treg cells are required for spinal cord, heart, and retina regeneration in zebrafish

  • Treg cells promote regeneration by producing tissue-specific growth factors

  • Pro-regenerative Treg cell activity is distinct from immunosuppressive functions

  • Zebrafish Foxp3a is essential for the production of tissue-specific growth factors

Summary

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.

Keywords

regeneration
spinal cord
heart
retina
neural stem cell
cardiomyocyte
regulatory T cell
zebrafish

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These authors contributed equally

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