Eosinophils secrete IL-4 to facilitate liver regeneration
Eosinophils secrete IL-4 to facilitate liver regeneration
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DOI：
10.1073/pnas.1304046110
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发表时间：
2013-06-11
影响因子：
11.1
通讯作者：
Chawla, Ajay
中科院分区：
文献类型：
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作者：
Goh, Y. P. Sharon;Henderson, Neil C.;Chawla, Ajay
肝脏是合成和储存营养物质、产生血清蛋白和激素以及分解毒素和代谢物的中心器官。由于肝脏易受毒素或病原体介导的损伤，因此它保持了通过补偿性生长进行再生的显著能力。具体地说，作为对损伤的响应，静止的肝细胞进入细胞周期并进行DNA复制以促进肝脏再生。尽管阐明了一些再生因子，肝损伤触发肝细胞增殖的机制还不完全清楚。我们在此证明嗜酸性粒细胞刺激肝部分切除术和毒素介导的损伤后的肝再生。肝损伤导致嗜酸性粒细胞的快速募集，其分泌IL-4以促进静止肝细胞的增殖。令人惊讶的是，通过巨噬细胞中的IL-4 R α的信号传导，其与组织修复有关，与损伤后的肝细胞增殖和肝脏再生有关。相反，IL-4通过肝细胞中的IL-4 R α发挥其增殖作用。因此，我们的研究结果提供了一个独特的机制，嗜酸性粒细胞衍生的IL-4刺激肝细胞增殖再生肝脏。
The liver is a central organ for the synthesis and storage of nutrients, production of serum proteins and hormones, and breakdown of toxins and metabolites. Because the liver is susceptible to toxin-or pathogen-mediated injury, it maintains a remarkable capacity to regenerate by compensatory growth. Specifically, in response to injury, quiescent hepatocytes enter the cell cycle and undergo DNA replication to promote liver regrowth. Despite the elucidation of a number of regenerative factors, the mechanisms by which liver injury triggers hepatocyte proliferation are incompletely understood. We demonstrate here that eosinophils stimulate liver regeneration after partial hepatectomy and toxin-mediated injury. Liver injury results in rapid recruitment of eosinophils, which secrete IL-4 to promote the proliferation of quiescent hepatocytes. Surprisingly, signaling via the IL-4R alpha in macrophages, which have been implicated in tissue repair, is dispensable for hepatocyte proliferation and liver regrowth after injury. Instead, IL-4 exerts its proliferative actions via IL-4R alpha in hepatocytes. Our findings thus provide a unique mechanism by which eosinophil-derived IL-4 stimulates hepatocyte proliferation in regenerating liver.