Understanding the cellular interactome of non-alcoholic fatty liver disease.
IF: 9.917
Cited by: 22


Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions, with a global prevalence of 25% in the adult population. Non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis, has become the leading indication for liver transplantation in both Europe and the USA. Liver fibrosis is the consequence of sustained, iterative liver injury, and the main determinant of outcomes in NASH. The liver possesses remarkable inherent plasticity, and liver fibrosis can regress when the injurious agent is removed, thus providing opportunities to alter long-term outcomes through therapeutic interventions. Although hepatocyte injury is a key driver of NASH, multiple other cell lineages within the hepatic fibrotic niche play major roles in the perpetuation of inflammation, mesenchymal cell activation, extracellular matrix accumulation as well as fibrosis resolution. The constituents of this cellular interactome, and how the various subpopulations within the fibrotic niche interact to drive fibrogenesis is an area of active research. Important cellular components of the fibrotic niche include endothelial cells, macrophages, passaging immune cell populations and myofibroblasts. In this review, we will describe how rapidly evolving technologies such as single-cell genomics, spatial transcriptomics and single-cell ligand-receptor analyses are transforming our understanding of the cellular interactome in NAFLD/NASH, and how this new, high-resolution information is being leveraged to develop rational new therapies for patients with NASH.


Spatial Transcriptomics
BAs, bile acids
CCL, C-C motif chemokine ligand
CCR, C-C motif chemokine receptor
CLD, chronic liver disease
CTGF, connective tissue growth factor
CXCL, C-X-C motif chemokine ligand
CXCR, C-X-C motif chemokine receptor
DAMP, damage-associated molecular pattern
ECM, extracellular matrix
ER, endoplasmic reticulum
FGF, fibroblast growth factor
FXR, farnesoid X receptor
HSCs, hepatic stellate cells
IL, interleukin
ILC, innate lymphoid cell
KCs, Kupffer cells
LSECs, liver sinusoidal endothelial cells
MAIT, mucosal-associated invariant T
MAMPS, microbiota-associated molecular patterns
NAFLD, non-alcoholic fatty liver disease
NASH, non-alcoholic steatohepatitis
NK(T), natural killer (T)
NLR, Nod like receptors
Non-alcoholic fatty liver disease (NAFLD)
PDGF, platelet-derived growth factor
PFs, portal fibroblasts
SASP, senescence-associated secretory phenotype
TGF, transforming growth factor
TLR, Toll-like receptor
TNF, tumour necrosis factor
VEGF, vascular endothelial growth factor
antifibrotic therapies
cellular interactome
single-cell genomics


Wallace, Sebastian J
Tacke, Frank
Schwabe, Robert F
Henderson, Neil C