The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-β) from latent complexes via integrin-α_V activation. Using acute injury models in two different tissues, we found that by inducing TGF-β activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.

表皮生长因子受体配体双调蛋白在损伤后恢复组织稳态中具有充分的作用；然而，双调蛋白有助于伤口修复的机制仍然未知。在这里，我们表明双调蛋白通过整合素-α _{V从潜在复合物中释放生物活性转化生长因子 β (TGF-β) 发挥作用}激活。在两种不同组织中使用急性损伤模型，我们发现通过诱导间充质基质细胞（周细胞）上的 TGF-β 活化，双调蛋白诱导它们分化为肌成纤维细胞，从而选择性地促进受损组织内血管屏障功能的恢复。此外，我们将巨噬细胞确定为双调蛋白的关键来源，揭示了这些细胞有助于急性损伤后组织恢复的直接效应机制。综合起来，这些观察揭示了免疫系统细胞在组织修复和炎症过程中如何选择性地控制组织祖细胞分化的机制，这一机制迄今未被充分认识。