The Spatiotemporal Accumulation of Myeloid Lineage Cells Is Mapping Out Fibrosis in the Liver after Acute and Chronic Injury

Liver fibrosis is known to become problematic after persistent injury. However, little is known about its response after an acute insult. Myeloid lineage cells, specifically, macrophages have been implicated in the promotion and resolution of inflammation and fibrosis. We investigated the role of myeloid lineage cells in the liver after acute injury. Our data show that thermal injury in mice induces fibrosis predominantly around portal venules whereas myeloid cells are enriched throughout the liver. The fibrosis peaks 1-2 weeks post injury and resolves by week 3. Depletion of myeloid cells led to lower fibrosis. Microarray analysis revealed an inflammatory signature and modulation of components of the serotonin (5-HT) pathway in myeloid cells. Antagonizing the 5HT2A/2C receptor decreased fibrosis in thermally injured mice, likely through promoting an anti-fibrotic phenotype in macrophages. Treating mice with a 5HT2A/2C receptor antagonist promotes an anti-fibrotic effect, through modulating the phenotype of macrophages.M.Sc