Proteomic analysis reveals a protective role of specific macrophage subsets in liver repair

ABSTRACT: Macrophages are a heterogeneous population of immune cells that play central roles in a broad range of biological processes, including the resolution of inflammation. Although diverse macrophage subpopulations have been identified, the characterization and functional specialization of certain macrophage subsets in inflamed tissues remain unclear. Here we uncovered a key role of specific macrophage subsets in tissue repair using proteomics, bioinformatics and functional analyses. We isolated two hepatic monocyte-derived macrophage subpopulations: Ly6ChiCX3CR1lo macrophages and Ly6CloCX3CR1hi macrophages during distinct phases of acute liver injury and employed label-free proteomics approach to profile the proteome of these cells. We found that the wound healing- and endocytosis-related proteins were specifically enriched in Ly6CloCX3CR1hi macrophages. Intriguingly, 12/15-lipoxygenase (Alox15), the most strongly up-regulated protein in Ly6CloCX3CR1hi macrophages, was identified as a specific marker for these macrophages. In co-culture systems, Ly6CloCX3CR1hi macrophages specifically induced hepatocyte proliferation. Furthermore, selective depletion of this population in CD11b-diphtheria toxin receptor mice significantly delayed liver repair. Overall, our studies shed light on the functional specialization of distinct macrophage subsets in the resolution of inflammation.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Macrophage

DISEASE(S): Liver Inflammation

SUBMITTER: Xinyuan Zhao  

LAB HEAD: Li Tang

PROVIDER: PXD011958 | Pride | 2019-10-08

REPOSITORIES: Pride