Liver fibrosis: cellular mechanisms of progression and resolution.
Liver fibrosis represents a major worldwide health care burden. The last 15 years have seen a rapid growth in our understanding of the pathogenesis of this clinically relevant model of inflammation and repair. This work is likely to inform the design of effective antifibrotic therapies in the near future. In this review, we examine how the innate and adaptive immune response interacts with other key cell types in the liver, such as the myofibroblast, regulating the process of hepatic fibrosis and, where relevant, resolution of fibrosis with remodelling. Emphasis is placed on the increasing knowledge that has been generated by the use of transgenic animals and animals in which specific cell lines have been deleted. Additionally, we review the increasing evidence that, although significant numbers of wound-healing myofibroblasts are derived from the hepatic stellate cell, significant contributions may occur from other cell lineages, including those from distant sites such as bone marrow stem cells.
Henderson
Neil C
NC
MRC/University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4TJ, U.K.
Iredale
John P
JP
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology*; D011379:Prognosis