Multispectral Imaging Differentiates Unique Macrophage Profiles in Patients with Distinct Chronic Liver Diseases
2019
Intrahepatic macrophages influence the composition of the microenvironment, host immune response to liver injury, and development of fibrosis. Compared to stellate cells, the role of intrahepatic macrophages in the development of fibrosis remains ill defined.
Multispectral imagingallows detection of multiple markers in situ in human formalin-fixed, paraffin-embedded tissue. This cutting-edge technology is ideal for analyzing human liver tissues since it allows spectral unmixing of fluorophore signals, subtraction of auto-fluorescence, and preserves architecture and the in vivo hepatic milieu. We analyzed resident
Kupffer cells(
CD68+), monocyte-derived macrophages (Mac387+), pro-fibrogenic macrophages (
CD163+), and co-expression of pro-inflammatory (CD14) and anti-inflammatory (
CD16) markers in
liver biopsiesfrom patients with hepatitis C virus (HCV) and different stages of fibrosis.
Liver biopsieswith advanced fibrosis showed increased accumulation of
CD163+, MAC387+ and
CD68+ macrophages in the
portal tractswhen compared to those with minimal fibrosis. Imaging software generated
t-distributed stochastic neighbor embedding(t-SNE) plots and phenotype matrices that facilitated comparison of macrophage profiles. These included monocyte-derived (
CD68+/Mac387+) and pro-fibrotic/anti-inflammatory (
CD163+/
CD16+) phenotypes. We established that the utility of this platform could be extended to
liver biopsiesfrom patients with other
chronic liver diseasesincluding nonalcoholic
steatohepatitisand
autoimmune hepatitis. Each disease exhibited a unique profile after
spectral imaginganalysis and this platform holds the potential to identify patients predisposed to progressive liver disease based on the macrophage composition. In summary,
spectral imagingis a powerful tool that enables analysis of macrophage profiles in different types of
chronic liver diseasesand has potential to change the manner in which we evaluate
liver biopsiesleading to more personalized treatment strategies.
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