| RRC ID |
54987
|
| 著者 |
Tsarouchas TM, Wehner D, Cavone L, Munir T, Keatinge M, Lambertus M, Underhill A, Barrett T, Kassapis E, Ogryzko N, Feng Y, van Ham TJ, Becker T, Becker CG.
|
| タイトル |
Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. 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. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
|
| 巻・号 |
9(1)
|
| ページ |
4670
|
| 公開日 |
2018-11-7
|
| DOI |
10.1038/s41467-018-07036-w
|
| PII |
10.1038/s41467-018-07036-w
|
| PMID |
30405119
|
| PMC |
PMC6220182
|
| MeSH |
Animals
Axons / metabolism
Collagen Type XII / metabolism
Inflammation Mediators / metabolism*
Interleukin-1beta / metabolism*
Macrophages / metabolism*
Microglia / metabolism
Microglia / pathology
Mutation / genetics
Nerve Regeneration*
Neutrophils / metabolism
Spinal Cord / metabolism*
Spinal Cord / pathology
Tumor Necrosis Factor-alpha / metabolism*
Zebrafish / immunology
Zebrafish / metabolism*
|
| IF |
11.878
|
| 引用数 |
31
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(6xTcf/LefBS-miniP:d2EGFP) |
