Regulatory T-cell remodeling across the HBV infection–cirrhosis continuum

Regulatory T cells (Tregs) have varied functions in the course of hepatitis B virus (HBV) infection and cirrhosis. Regulatory T cells (Tregs) generally restrict excessive immune-mediated liver injury in acute HBV infection but may also inhibit antiviral immunity. During chronic infection, expanded and intrahepatically enriched Tregs suppress HBV-specific effector T-cell responses, maintain antiviral immune hyporesponsiveness and viral persistence, and limit chronic necroinflammatory injury. As the extent of HBV-related liver fibrosis progresses, there is a relative deficiency in both Tregs and Th17 cells. Treg cells are not only inhibitory to fibrosis; they are also interconnected with the immune-fibrotic microenvironment established by HSCs, and inflammation, HSC activation, extracellular matrix deposition and Treg/Th17 imbalance are all interrelated. Tregs in HBV-associated cirrhosis are highly heterogeneous, compartmentally distributed, functionally reprogrammed, and have joined an intrahepatic immunosuppressive-fibrotic network that includes myeloid cells, HSCs, natural killer cells, CD8+ T cells and Th17 cells. This paper will introduce modifications in Treg abundance, phenotype, distribution and function during the progressive alteration of these periods, as well as microenvironmental factors, Treg/Th17 dysregulation and specific therapeutic options. Therefore, the effect of regulation of Treg activity in HBV-associated liver disease is context-dependent and stage-specific, not uniform enhancement or suppression.