The regenerative capacity of human organs is inherently limited, and this ability diminishes progressively with aging as well as during disease, negatively impacting the post-organ injury consequences. For example, upon myocardial infarction, muscle tissue is lost and permanently replaced by scar tissue, leading to the functional decline of the heart. The type, timing, and orchestration of the immune response to injury strongly influence the spectrum of regenerative outcomes post-organ injury. In particular, the adaptive immune system, with T cells as key regulators, exerts significant influence over the delicate balance between organ regeneration or tissue damage. While adverse adaptive immune responses lead to poor regenerative outcomes, beneficial ones are needed to stimulate regenerative programs, and the balance between such responses varies throughout life. Moreover, the memory properties and adaptive nature of this type of immunity make it a unique and promising platform to be harnessed for immunomodulation strategies towards sustaining organ regeneration.

In contrast to mammals, fish species, such as the zebrafish, hold an incredible capacity to regenerate multiple organs, including the heart and the fin, making them excellent models to understand the cellular and molecular mechanisms underlying organ regeneration. In addition, zebrafish offer unique advantages due to their amenability for genome editing, facilitating the generation of essential tailored genetic tools to study organ regeneration.