Immunoregulation of Liver Fibrosis: New Opportunities for Antifibrotic Therapy

Liver fibrosis develops in response to chronic liver injury and is characterized by a sustained inflammatory response that leads to excessive collagen deposition by myofibroblasts. The fibrogenic response is governed by the release of inflammatory mediators from innate, adaptive, and innate-like lymphoid cells and from nonprofessional immune cells (i.e., epithelial cells, hepatic myofibroblasts, and liver sinusoidal endothelial cells). Upon removal of the underlying cause, liver fibrosis can resolve via activation of specific immune cell subsets. Despite major advances in the understanding of fibrosis pathogenesis, there is still no approved antifibrotic therapy. This review summarizes our current knowledge of the immune cell landscape and the inflammatory mechanisms underlying liver fibrosis progression and regression. We discuss how reprogramming immune cell phenotype, in particular through targeting selective inflammatory pathways or modulating cell-intrinsic metabolism, may be translated into antifibrogenic therapies.