The molecular interplay between progenitors and immune cells in tissue regeneration and homeostasis

Objectives

Some vertebrates in the animal kingdom including salamanders and teleost fish have the astonishing ability to fully regenerate many appendages and organs throughout their lifespan. In contrast, most mammals exhibit limited regenerative capabilities that decline with age. Over the last decade, cells in both the innate and adaptive immune system have emerged as key players that direct successful appendage and organ regenerative outcomes. Furthermore, recent studies have highlighted the importance of communication between damaged tissues and the immune system for orchestration of a pro-regenerative response. Understanding the differences in immune response to tissue injury between regenerative and non-regenerative organisms may therefore help inform efforts to stimulate regenerative abilities in humans.

Key findings

This review summarizes present knowledge of the known roles of both the innate and adaptive immune system in the regeneration of organs and appendages in highly regenerative species, with a particular focus on macrophages and T-cells. Furthermore, recent studies showing the importance of communication between the immune system and stem or progenitor cells during tissue homeostasis and regeneration are highlighted. Finally, as cells in the immune system have highly plastic phenotypes depending on their micro-environment, this review sheds light on the possibility that intrinsic differences in tissue damage responses may be the main driver of divergent immune responses in regenerative vs. non-regenerative systems.

Conclusions

Altogether, insights from these studies illustrate the need to fully examine not only the immune cells, but also the micro-environment to which they are exposed, as there may be both important cues from non-immune cells and intrinsic differences in how damaged tissues respond to injury between regenerative and non-regenerative organisms.