Author:
Sanchez Vasquez Juan Diego,Nkongolo Shirin,Traum Daniel,Kim Samuel C.,Mahamed Deeqa,Mehrotra Aman,Patel Anjali,Chen Diana,Fung Scott,Gaggar Anuj,Feld Jordan J.,Chang Kyong-Mi,Wallin Jeffrey J.,Janssen Harry L.A.,Gehring Adam J.
Abstract
AbstractChronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating in an inflammatory environment can potentially imprint a phenotype that switches the liver from an immunotolerant organ to one predisposed to tissue damage. We longitudinally sampled the liver of chronic hepatitis B (CHB) patients with active liver inflammation starting antiviral therapy. Antiviral therapy suppressed viral replication and liver inflammation, which coincided with decreased myeloid activation markers. Single-cell RNA sequencing mapped peripheral inflammatory markers to a monocyte-derived macrophage population, distinct from Kupffer cells, with an inflammatory transcriptional profile. The inflammatory macrophages (iMacs) differentiated from blood monocytes and established a long-lived population. The iMacs retained their core transcriptional signature, consistent with trained immunity, resulting in a population of macrophages primed for inflammation potentially driving progressive liver disease.
Publisher
Cold Spring Harbor Laboratory