Regeneration, tissue injury and the immune response

Abstract

The involvement of the immune system in the response to tissue injury has raised the possibility that it might influence tissue, organ or appendage regeneration following injury. One hypothesis that has been discussed is that inflammatory aspects may preclude the occurrence of regeneration, but there is also evidence for more positive roles of immune components. The vertebrate eye is an immunoprivileged site where inflammatory aspects are inhibited by several immunomodulatory mechanisms. In various newt species the ocular tissues such as the lens are regenerative and it has recently been shown that the response to local injury of the lens involves activation of antigen-presenting cells which traffic to the spleen and return to displace and engulf the lens, thereby inducing regeneration from the dorsal iris. The activation of thrombin from prothrombin in the dorsal iris is one aspect of the injury response that is important in the initiation of regeneration. The possible relationships between the immune response and the regenerative response are considered with respect to phylogenetic variation of regeneration in general, and lens regeneration in particular.

Mechanisms of urodele limb regeneration

“…Urodeles, which can regenerate limbs as larvae and adults, have a much less developed immune system than anurans (frogs and toads), which regenerate limbs only as early tadpoles, and mammals, which have no limb regenerative power except for digit tips. Macrophages are particularly important for the events of blastema formation during urodele limb regeneration (Godwin & Brockes, 2006; Godwin & Rosenthal, 2014; Mescher, 2017; Mescher et al, 2017; for reviews).…”

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…The site of injury produces a number of soluble mediators that influence resident-cell fate and initiate tissue-and injury-specific immune responses. These processes are critical for tissue regeneration and repair (Eming et al, 2007;Godwin and Brockes, 2006). In this section, we review the recruitment of MSCs and pericytes to the site of injury, and the soluble mediators responsible for this process.…”

Looking proximally and distally: 100 years of limb regeneration and beyond

“…Two main ideas have emerged. The first is that the regenerative program is suppressed in adult frogs, birds, and mammals as the immune system matures during development and the limb buds shift to a faulty regeneration response that is associated with a more intense inflammatory response to amputation (for review, see Harty et al, 2003;Mescher andNeff, 2005, 2006;Godwin and Brockes, 2006). Evidence supporting this idea is that urodeles do have a more primitive immune system than Xenopus (Cohen, 1971;Dupasquier and Flajnik, 1999) and that the immune system of Xenopus changes profoundly during tadpole development, coincident with loss of limb regenerative capacity.…”