The myeloid lineage is required for the emergence of a regeneration permissive environment following Xenopus tail amputation

Abstract

Regeneration-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 -competent tadpoles. We then reveal that upon tail amputation, myeloid lineage reduces apoptosis levels which in turn promotes tissue remodeling, 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 restore 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 can be further exploited to devise strategies for regenerative medicine purposes.