PUBLICATION
An anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury in zebrafish
- Authors
- Denans, N., Tran, N.T.T., Swall, M.E., Diaz, D.C., Blanck, J., Piotrowski, T.
- ID
- ZDB-PUB-220922-8
- Date
- 2022
- Source
- Nature communications 13: 5356 (Journal)
- Registered Authors
- Piotrowski, Tatjana
- Keywords
- none
- Datasets
- GEO:GSE209884
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/metabolism
- Anti-Inflammatory Agents/pharmacology
- Glucocorticoids/metabolism
- Inflammation/genetics
- Inflammation/metabolism
- Interleukin-10*/genetics
- Interleukin-10*/metabolism
- Interleukin-4/genetics
- Interleukin-4/metabolism
- Macrophages/metabolism
- Polyamines/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 36127326 Full text @ Nat. Commun.
Citation
Denans, N., Tran, N.T.T., Swall, M.E., Diaz, D.C., Blanck, J., Piotrowski, T. (2022) An anti-inflammatory activation sequence governs macrophage transcriptional dynamics during tissue injury in zebrafish. Nature communications. 13:5356.
Abstract
Macrophages are essential for tissue repair and regeneration. Yet, the molecular programs, as well as the timing of their activation during and after tissue injury are poorly defined. Using a high spatio-temporal resolution single cell analysis of macrophages coupled with live imaging after sensory hair cell death in zebrafish, we find that the same population of macrophages transitions through a sequence of three major anti-inflammatory activation states. Macrophages first show a signature of glucocorticoid activation, then IL-10 signaling and finally the induction of oxidative phosphorylation by IL-4/Polyamine signaling. Importantly, loss-of-function of glucocorticoid and IL-10 signaling shows that each step of the sequence is independently activated. Lastly, we show that IL-10 and IL-4 signaling act synergistically to promote synaptogenesis between hair cells and efferent neurons during regeneration. Our results show that macrophages, in addition to a switch from M1 to M2, sequentially and independently transition though three anti-inflammatory pathways in vivo during tissue injury in a regenerating organ.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping