Zebrafish Regulatory T Cells Mediate Organ-Specific Regenerative Programs.

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 T_reg-like (zT_reg) cells rapidly homed to damaged organs. Conditional ablation of zT_reg cells blocked organ regeneration by impairing precursor cell proliferation. In addition to modulating inflammation, infiltrating zT_reg 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 zT_reg cell depletion, whereas Foxp3a-deficient zT_reg cells infiltrated damaged organs but failed to express regenerative factors. Our data delineate organ-specific roles for T_reg cells in maintaining pro-regenerative capacity that could potentially be harnessed for diverse regenerative therapies.

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