PUBLICATION

M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery

Authors
Li, Z., Xiao, J., Xu, X., Li, W., Zhong, R., Qi, L., Chen, J., Cui, G., Wang, S., Zheng, Y., Qiu, Y., Li, S., Zhou, X., Lu, Y., Lyu, J., Zhou, B., Zhou, J., Jing, N., Wei, B., Hu, J., Wang, H.
ID
ZDB-PUB-210314-1
Date
2021
Source
Science advances   7(11): (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Brain Injuries, Traumatic*
  • Humans
  • Interleukin-6/genetics
  • Macrophage Colony-Stimulating Factor*
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Transforming Growth Factor beta
  • Zebrafish
PubMed
33712456 Full text @ Sci Adv
Abstract
Traumatic brain injury (TBI) leads to high mortality rate. We aimed to identify the key cytokines favoring TBI repair and found that patients with TBI with a better outcome robustly increased concentrations of macrophage colony-stimulating factor, interleukin-6, and transforming growth factor-β (termed M6T) in cerebrospinal fluid or plasma. Using TBI mice, we identified that M2-like macrophage, microglia, and endothelial cell were major sources to produce M6T. Together with the in vivo tracking of mCherry+ macrophages in zebrafish models, we confirmed that M6T treatment accelerated blood-borne macrophage infiltration and polarization toward a subset of tissue repair macrophages that expressed similar genes as microglia for neuroprotection, angiogenesis and cell migration. M6T therapy in TBI mice and zebrafish improved neurological function while blocking M6T-exacerbated brain injury. Considering low concentrations of M6T in some patients with poor prognostic, M6T treatment might repair TBI via generating a previously unidentified subset of tissue repair macrophages.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping