RT Journal Article
SR Electronic
T1 Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 332197
DO 10.1101/332197
A1 Themistoklis M. Tsarouchas
A1 Daniel Wehner
A1 Leonardo Cavone
A1 Tahimina Munir
A1 Marcus Keatinge
A1 Marvin Lambertus
A1 Anna Underhill
A1 Thomas Barrett
A1 Elias Kassapis
A1 Nikolay Ogryzko
A1 Yi Feng
A1 Tjakko J. van Ham
A1 Thomas Becker
A1 Catherina G. Becker
YR 2018
UL http://biorxiv.org/content/early/2018/05/28/332197.1.abstract
AB Spinal cord injury leads to a massive response of innate immune cells (microglia, macrophages, neutrophils) both, in non-regenerating mammals and in successfully regenerating zebrafish, but the role of these immune cells in functional spinal cord regeneration in zebrafish has not been addressed. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in larval zebrafish. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary and sufficient for full regeneration. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Il-1β and Tnf-α. Decreasing Il-1β levels or number of Il-1β+ neutrophils rescues functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. Hence, inflammation is tightly and dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.