Epimorphic Regeneration: an Immunological Perspective
Anton W. Neff1,3, Mark, W. Harty1, Michael C. Muzinich1, Wendy L. Wolf1, Michael W. King2,3, and Anthony L. Mescher1,3
Epimorphic regeneration (ER), i.e., regeneration of vertebrate complex patterned tissues and organs to their previous uninjured state can be considered a perfect wound healing and tissue/organ repair process without scarring. ER occurs in adult urodeles, larval anurans, teleosts, and in MRL mice and historically the premier model system for ER has been limb regeneration. The cardinal characteristic of ER is the establishment of a regeneration blastema that is able to recapitulate ontogenesis of the missing organ. ER is a complex process involving overlapping phases such as wound healing, dedifferentiation, cell proliferation, repatterning, and cell differentiation. Even though there is considerable evidence for the importance of immune system cells and mediators (e.g. cytokines) in mammalian wound healing and tissue repair the role of the immune system in positively or negatively regulating ER has received little attention. We review evidence for the involvement of the innate and adaptive immune systems in ER and address the problems of dealing with the complexity of immunoregulation and the problem of deciphering immune versus non-immune functions of immunoregulators. We discuss the idea that ER-competence may involve peripheral immunotolerence. We propose comparative molecular and cellular immunostudies comparing ER-competent versus ER-incompetent model systems such as: ear hole repair in MRL mice versus poor wound healing strains of mice, limb regeneration in adult urodeles versus anurans, and larval versus prometamorphic anurans.
1 Medical Sciences Program, IU School of Medicine, Indiana University, Bloomington IN
2 Center for Medical Education, IU School of Medicine, Terre Haute, IN
3 Center for Regenerative Biology and Medicine, IUPUI, Indianapolis IN