Intrahepatic TH17/TReg Cells in Homeostasis and Disease-It's All About the Balance

Abstract

Both acute and chronic hepatic inflammation likely result from an imbalance in the T_H1/T_H2 cell response and can lead to liver fibrosis and end-stage liver disease. More recently, a novel CD4+ T helper cell subset was described, characterized by the production of IL-17 and IL-22. These T_H17 cells 50were predominantly implicated in host defense against infections and in autoimmune diseases. Interestingly, studies over the last 10 years revealed that the development of T_H17 cells favors pro-inflammatory responses in almost all tissues and there is a reciprocal relationship between T_H17 and T_Reg cells. The balance between T_H17and T_Reg cells is critical for immune reactions, especially in injured liver tissue and the return to immune homeostasis. The pathogenic contribution of T_H17 and T_Reg cells in autoimmunity, acute infection, and chronic liver injury is diverse and varies among disease etiologies. Understanding the mechanisms underlying T_H17 cell development, recruitment, and maintenance, along with the suppression of T_Reg cells, will inform the development of new therapeutic strategies in liver diseases. Active manipulation of the balance between pathogenic and regulatory processes in the liver may assist in the restoration of homeostasis, especially in hepatic inflammation.

Keywords: TH17 cells; TH17/TReg balance; TReg cells; autoimmune diseases; liver; viral infection.