Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs

Publication date: 18 December 2017
Source:Developmental Cell, Volume 43, Issue 6
Author(s): Subhra P. Hui, Delicia Z. Sheng, Kotaro Sugimoto, Alvaro Gonzalez-Rajal, Shinichi Nakagawa, Daniel Hesselson, Kazu Kikuchi
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.

Teaser

Hui et al. show that zebrafish regulatory T (zTreg) cells infiltrate damaged spinal cords, hearts, and retinas and are essential for robust regeneration. Infiltrating zTreg cells produce tissue-specific pro-regenerative factors that stimulate tissue-resident precursor cell proliferation, revealing new cellular targets for increasing regenerative capacity in poorly regenerating species.


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