Macrophages are required for adult salamander limb regeneration
Macrophages are required for adult salamander limb regeneration
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DOI：
10.1073/pnas.1300290110
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发表时间：
2013-06-04
影响因子：
11.1
通讯作者：
Rosenthal, Nadia A.
中科院分区：
文献类型：
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作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
在成年哺乳动物中，不能替换受损的身体部位是由于生长反应减弱和纤维化疤痕造成的。尽管浸润性免疫细胞在决定哺乳动物伤口修复的可变结果中起着重要作用，但对免疫细胞信号在有效再生物种（如蝾螈）中的调节知之甚少，蝾螈可以在成年后再生完整的身体结构。在这里，我们全面分析了蝾螈肢体再生过程中的免疫信号，并揭示了再生过程中巨噬细胞浸润的时间定义需求。尽管蝾螈保留了哺乳动物细胞因子/趋化因子信号的许多特征，但它们的部署更加动态，在截肢后的前24小时内同时诱导炎症和抗炎标志物。在此期间，全身巨噬细胞的消耗导致伤口愈合，但肢体再生的永久性失败，与广泛的纤维化和细胞外基质成分基因表达失调有关。一旦内源性巨噬细胞群得到补充，断肢的完全肢体再生能力可以通过再截肢恢复。因此，通过鉴定巨噬细胞来源的治疗分子来促进允许再生的环境可能有助于成年哺乳动物受损身体部位的再生。
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.