.png){kind=icon}
.png){kind=icon}
Return
Lipid-dependent accrual of a subset of monocyte-derived macrophages is essential for tissue regeneration
.png){kind=icon}
PRE
AI
T
X
L
J
J
H
Y
X
X
L
B
Y
D
S
H
Z
X
S
M
B
Y
DOI：10.1038/s42255-026-01480-5.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Tissue regeneration is essential for maintaining tissue homoeostasis and influences disease progression. In the liver, injury evokes a complex regenerative response with robust immune activation and metabolic rewiring, yet how these processes coordinate hepatocyte proliferation remains unclear. Here we show the presence of an injury-induced, lipid-dependent accrual of a distinct monocyte-derived macrophage (MDM) subset characterized by abundant cytosolic lipid content and heightened inflammatory response. Multi-omic analyses, spanning both single-cell transcriptomics and quantitative lipidomics, unveil substantial cellular diversity and heterogeneity between these ‘lipo-inflammatory MDMs’ (termed LIMMs) and other hepatic macrophages, including Kupffer cells. Blocking CD36-dependent LIMM induction markedly impairs hepatocyte proliferation and liver regeneration in injured livers. Mechanistically, CD36-mediated increase in ceramide biosynthesis activates IRE1α–XBP1 signalling pathway in LIMMs, driving production of the regenerative cytokine interleukin-6. Disrupting CD36-dependent IRE1α activation in LIMMs compromises liver repair. These findings identify a lipid-laden MDM subcluster as a key regulator of regenerative inflammation in injured livers. A distinct lipid-laden subset of monocyte-derived macrophages regulates hepatocyte proliferation and liver regeneration in injured livers, via CD36-mediated signalling.
Keywords:
Fat metabolism
Liver
Metabolism
Monocytes and macrophages
Stress signalling
Life Sciences
general
Journal
IF:
20.8
Papers:
1.6K
Citations:
1.4W
Organization
Cited Papers