Acute and chronic hepatic inflammation subsequently leading to liver fibrosis and end-stage liver disease is believed to be the consequence of an imbalance of the TH1/TH2 cell response. More recently, a new CD4+ T helper cell subset was discovered mainly characterized by the production of IL-17 and IL-22. Initially, these TH17 cells were found to be predominantly involved in the host defense against infections and in autoimmune diseases. Extensive studies over the past 10 years revealed that the development of TH17 cells favors pro-inflammatory responses in almost all tissues and that a reciprocal relationship between TH17 and TReg cells exists. This balance between TH17and TReg cells is critical for immune reactions especially in injured liver tissue and the recovery to immune homeostasis. The pathogenic contribution of TH17 and TReg cells in autoimmunity, acute infection and chronic liver injury is divers and varies in different disease etiologies. Understanding the mechanisms which promote TH17 cell development, recruitment and maintenance and at the same time suppress TReg cells is crucial for potential new therapeutic strategies in liver diseases. Active manipulation of the balance between pathogenic and regulatory processes in the liver is thought to allow the focused restoration of homeostasis especially during hepatic inflammation.

T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (T_RM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic T_RM cells can reside within the liver tissue for several years. Interestingly, hepatic T_RM cell differentiation requires a distinct cytokine milieu. In addition, T_RM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver T_RM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic T_RM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies.