Exploring Sex Differences in Liver Fibrosis and Regression, and the Role of MAIT Cells in Regeneration

The PhD thesis is divided into two parts, reflecting my PhD journey between the University of Padova and Oxford. I began my PhD by investigating sex-related differences in the development and regression of liver fibrosis, and associated sarcopenia using progressive dosages of the hepatotoxic agent carbon tetrachloride (CCl4). Our model successfully induced chronic liver damage, revealing that males experienced earlier disease onset, while females were more susceptible to chronic damage. Throughout the disease progression, pro-inflammatory processes in the liver led to sarcopenia, also known as muscle wasting, in both sexes. Notably, after recovery period from induced liver damage, female livers regenerated better than males, while male muscles recovered more effectively than female muscles. Considering the major role of T cells in mediating liver regeneration, especially unconventional T cells, I further explored the role of MAIT cells in tissue repair, at the University of Oxford. We found that MAIT cells uniquely produce VEGF, and vimentin only upon activation, promoting tissue regeneration through their interaction with VEGFR-2, a receptor that mediates cell proliferation.