Hasegawa Tomoya, Hall Christopher J, Crosier Philip S, Abe Gembu, Kawakami Koichi, Kudo Akira, Kawakami Atsushi
School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Japan.
Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand.
Elife. 2017 Feb 23;6:e22716. doi: 10.7554/eLife.22716.
Cellular responses to injury are crucial for complete tissue regeneration, but their underlying processes remain incompletely elucidated. We have previously reported that myeloid-defective zebrafish mutants display apoptosis of regenerative cells during fin fold regeneration. Here, we found that the apoptosis phenotype is induced by prolonged expression of (). Myeloid cells are considered to be the principal source of Il1b, but we show that epithelial cells express in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for survival of regenerative cells. We further show that Il1b plays an essential role in normal fin fold regeneration by regulating expression of regeneration-induced genes. Our study reveals that proper levels of Il1b signaling and tissue inflammation, which are tuned by macrophages, play a crucial role in tissue regeneration.
细胞对损伤的反应对于组织的完全再生至关重要，但其潜在机制仍未完全阐明。我们之前报道过，骨髓缺陷型斑马鱼突变体在鳍褶再生过程中表现出再生细胞的凋亡。在此，我们发现凋亡表型是由（）的长期表达所诱导的。髓样细胞被认为是Il1b的主要来源，但我们发现上皮细胞在组织损伤时会表达（）并启动炎症反应，而巨噬细胞对其炎症反应的消退对于再生细胞的存活是必要的。我们进一步表明，Il1b通过调节再生诱导基因的表达在正常鳍褶再生中发挥重要作用。我们的研究揭示，由巨噬细胞调节的适当水平的Il1b信号传导和组织炎症在组织再生中起着关键作用。
