Bidirectional role of NKT cells in the development of autoimmune hepatitis and hepatocellular carcinoma

Trabajo fin de máster presentado en la Universidad Autónoma de Barcelona, Master in Translational Biomedical Research.--Calificación: 9.23Chronic liver disease includes several clinical entities, such as non-alcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC). All of them have a key immunological component, so they are influenced by the special immune composition of the liver. Moreover, most of these pathologies are clearly sex-biased, but the underlying mechanisms are not well understood. In this respect, NKT cells are a compelling object of study, since they are predominantly located in the liver. In this project, NKT cell-deficient mice (CD1d-KO) were used to assess the differences within two models of chronic liver disease. Concanavalin A (ConA) injection was used as a model of autoimmune hepatitis and diethylnitrosamine plus high-fat choline deficient diet (DEN + HFCD) was used as a model for hepatocellular carcinoma. The first objective of the project was to analyze the effects of NKT-depletion in these two models, and the second objective was to observe whether these effects were different between male and female mice. For the DEN + HFCD model, CD1d-KO mice were observed to have a worse outcome, with a higher number of tumors, a more severe stage of the disease and an increase in the expression of tumor markers. Furthermore, WT females appeared to be more naturally resistant to HCC, but CD1d-KO females had lost that resistance, indicating that NKT cells could be a protective factor for females against HCC. In short, this project revealed that NKT cells are involved in the development of chronic liver disease. In addition, some of the results pointed that NKT cells might have differential roles depending on the sex