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.
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.
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Human Disease / Model
Sequence Targeting Reagents
Fish
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Mapping