Macrophages are required for adult salamander limb regeneration

James Walter Godwin, Ruvantha Ignatius Alexander Pinto, Nadia Alicia Rosenthal

Research output: Contribution to journalArticleResearchpeer-review

309 Citations (Scopus)

Abstract

The failure to replace damaged body parts in adult mammals results from a muted growth response and fibrotic scarring. Although infiltrating immune cells play a major role in determining the variable outcome of mammalian wound repair, little is known about the modulation of immune cell signaling in efficiently regenerating species such as the salamander, which can regrow complete body structures as adults. Here we present a comprehensive analysis of immune signaling during limb regeneration in axolotl, an aquatic salamander, and reveal a temporally defined requirement for macrophage infiltration in the regenerative process. Although many features of mammalian cytokine/chemokine signaling are retained in the axolotl, they are more dynamically deployed, with simultaneous induction of inflammatory and anti-inflammatory markers within the first 24 h after limb amputation. Systemic macrophage depletion during this period resulted in wound closure but permanent failure of limb regeneration, associated with extensive fibrosis and disregulation of extracellular matrix component gene expression. Full limb regenerative capacity of failed stumps was restored by reamputation once endogenous macrophage populations had been replenished. Promotion of a regeneration-permissive environment by identification of macrophage-derived therapeutic molecules may therefore aid in the regeneration of damaged body parts in adult mammals.
Original languageEnglish
Pages (from-to)9415 - 9420
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume110
Issue number23
DOIs
Publication statusPublished - 2013

Cite this

Godwin, James Walter ; Pinto, Ruvantha Ignatius Alexander ; Rosenthal, Nadia Alicia. / Macrophages are required for adult salamander limb regeneration. In: Proceedings of the National Academy of Sciences. 2013 ; Vol. 110, No. 23. pp. 9415 - 9420.
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Macrophages are required for adult salamander limb regeneration. / Godwin, James Walter; Pinto, Ruvantha Ignatius Alexander; Rosenthal, Nadia Alicia.

In: Proceedings of the National Academy of Sciences, Vol. 110, No. 23, 2013, p. 9415 - 9420.

Research output: Contribution to journalArticleResearchpeer-review

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