Abstract
ABSTRACTRegeneration-competent vertebrates are considered to suppress inflammation faster than non-regenerating ones. Hence, understanding the cellular mechanisms affected by immune cells and inflammation can help develop strategies to promote tissue repair and regeneration. Here, we took advantage of naturally occurring tail regeneration-competent and -incompetent developmental stages of Xenopus tadpoles. We first establish the essential role of the myeloid lineage for tail regeneration in the regeneration-competent tadpoles. We then reveal that upon tail amputation there is a myeloid lineage-dependent change in amputation-induced apoptosis levels, which in turn promotes tissue remodelling, and ultimately leads to the relocalization of the regeneration-organizing cells responsible for progenitor proliferation. These cellular mechanisms failed to be executed in regeneration-incompetent tadpoles. We demonstrate that regeneration incompetency is characterized by inflammatory myeloid cells whereas regeneration competency is associated with reparative myeloid cells. Moreover, treatment of regeneration-incompetent tadpoles with immune-suppressing drugs restores myeloid lineage-controlled cellular mechanisms. Collectively, our work reveals the effects of differential activation of the myeloid lineage on the creation of a regeneration-permissive environment and could be further exploited to devise strategies for regenerative medicine purposes.
Highlights
Regeneration-competent vertebrates are considered to have a limited immune system development and competency (Julier et al, 2017)
The myeloid lineage is required for Xenopus tail regeneration We first asked whether the myeloid lineage is required for regeneration by injecting clodronate-containing liposomes into the ventral vein area of tadpoles (Fig. 1A) assessing regeneration ability after tail amputation
Upon tail amputations, these tadpoles had a reduced tail regeneration compared with control, Encapsome-injected animals (Fig. 1D, Fig. S1B), suggesting the myeloid lineage is required for regeneration
Summary
Regeneration-competent vertebrates are considered to have a limited immune system development and competency (Julier et al, 2017). The immune system has been demonstrated to influence regeneration positively in various scenarios, e.g. in appendages (Godwin et al, 2013; Petrie et al, 2014) and in cardiac tissue (Godwin et al, 2017; Lavine et al, 2014), and in several. Regeneration-incompetent animals have a prolonged inflammatory phase that results in an impairment of extracellular matrix remodelling mediated by excessive collagen deposition and scar formation (Godwin, 2014). In such animals, suppression of inflammation improves injury repair and regeneration (Chu et al, 2019; Gensel et al, 2017). An overall understanding of the cellular events controlled by the inflammatory states and their effect in animals with high regenerative capabilities is lacking
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