Liver Regeneration and Immunity: A Tale to Tell
Nicola Di-Iacovo, Stefania Pieroni, Danilo Piobbico, Marilena Castelli, Damiano Scopetti, Simona Ferracchiato, Maria Agnese Della Fazia, Giuseppe Servillo
Abstract
The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.