Figure 7. Proposed mechanism for the induction of immune tolerance in livers with a disrupted intestinal barrier.

The liver is exposed to gut-derived antigens through the portal vein. In steady state conditions, hepatic inflammatory macrophages play a critical role in their elimination. In the presence of a disrupted intestinal barrier, continuous exposure to microbe-associated molecular patterns increases NNMT expression, along with a concomitant increase in 1-MNA levels, and shifts hepatic inflammatory macrophages to a regulatory phenotype accompanied by potential IL-10 production in response to further stimulation to avoid excessive tissue damage. MAMPS, microbe-associated molecular patterns.