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Zebrafish regulatory T cells mediate organ-specific regenerative programs

Abstract

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 novel 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 pro-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 novel organ-specific roles for Treg cells in maintaining pro-regenerative capacity that could potentially be harnessed for diverse regenerative therapies.

Type Journal
Authors Subhra P. Hui1, Delicia Z. Sheng1a , Kotaro Sugimoto1a , Alvaro Gonzalez-Rajal1, Shinichi Nakagawa2,3, Daniel Hesselson3,4, and Kazu Kikuchi1,4*
Responsible Garvan Author Dr Daniel Hesselson
Publisher Name DEVELOPMENTAL CELL
Published Date 2017-12-18
Published Volume 43
Published Issue 6
Published Pages 659-672 e5
Status Published in-print
DOI 10.1186/s12915-017-0448-5
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679152/