Immunity in salamander regeneration: Where are we standing and where are we headed?

Abstract

Salamanders exhibit the most extensive regenerative repertoire among vertebrates, being able to accomplish scar-free healing and faithful regeneration of significant parts of the eye, heart, brain, spinal cord, jaws and gills, as well as entire appendages throughout life. The cellular and molecular mechanisms underlying salamander regeneration are currently under extensive examination, with the hope of identifying the key drivers in each context, understanding interspecies differences in regenerative capacity, and harnessing this knowledge in therapeutic settings. The immune system has recently emerged as a potentially critical player in regenerative responses. Components of both innate and adaptive immunity have been found at critical stages of regeneration in a range of salamander tissues. Moreover, functional studies have identified a requirement for macrophages during heart and limb regeneration. However, our knowledge of salamander immunity remains scarce, and a thorough definition of the precise roles played by its members is lacking. Here, we examine the evidence supporting roles for immunity in various salamander regeneration models. We pinpoint observations that need revisiting through modern genetic approaches, uncover knowledge gaps, and highlight insights from various model organisms that could guide future explorations toward an understanding of the functions of immunity in regeneration.

Study of Natural Longlife Juvenility and Tissue Regeneration in Caudate Amphibians and Potential Application of Resulting Data in Biomedicine

“…It is currently known that the ancient and highly conservative immune system can not only regulate, but also be directly involved in tissue regeneration in animals, including caudate amphibians [ 3 , 4 ]. Its relationship to the processes of regeneration of various tissues and organs in salamanders is considered in detail in a recent review [ 4 ].…”

“…It is currently known that the ancient and highly conservative immune system can not only regulate, but also be directly involved in tissue regeneration in animals, including caudate amphibians [ 3 , 4 ]. Its relationship to the processes of regeneration of various tissues and organs in salamanders is considered in detail in a recent review [ 4 ]. According to the summarized information, the innate and adaptive components of the immune system in the Urodela are found at critical stages of regeneration of many tissues, from the moment of damage to the morphogenesis of newly formed regenerates.…”

“…The role of macrophages, the direct participants in the regeneration of the heart and limb of these animals, is also reported. Particular attention is paid to the complement system and its plasma proteins, which also play a significant role in the regeneration processes [ 4 ].…”

Salamander models for elucidating mechanisms of developmental biology, evolution, and regeneration: Part one

“…Immune system inputs and controls on regenerative processes are becoming increasingly appreciated in a variety of model systems, salamanders included. A thorough review, and insightful consideration of future directions, on the topic of how the immune system regulates regenerative responses in salamanders is presented by Bolanos-Castro et al 8 One fascinating aspect of salamander biology is the massive size of their genomes which can range anywhere between 14 and 120 Gb. This feature provides challenges to regenerative processes, but also may play a mechanistic role itself.…”

“…Immune system inputs and controls on regenerative processes are becoming increasingly appreciated in a variety of model systems, salamanders included. A thorough review, and insightful consideration of future directions, on the topic of how the immune system regulates regenerative responses in salamanders is presented by Bolanos‐Castro et al 8 …”