Hasegawa, T., Hall, C.J., Crosier, P.S., Abe, G., Kawakami, K., Kudo, A., Kawakami, A. (2017) Transient inflammatory response mediated by interleukin-1β is required for proper regeneration in zebrafish fin fold. eLIFE. 6.
Cellular responses to injury are recognized to be 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 the prolonged expression of interleukin 1 beta (il1b). Myeloid cells have been considered to be the principal source of Il1b, but we show that epithelial cells express il1b in response to tissue injury and initiate the inflammatory response, and that its resolution by macrophages is necessary for the survival of regenerative cells. We further show that Il1b also plays an essential role in normal fin fold regeneration by regulating the 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.