In a different project we are also interested in examining whether the gut microbiota plays a role in the development of autoimmune hepatitis (AIH) in the liver.  Gut components drain to the liver through the portal circulation. These include immune-cells, pro-inflammatory cytokines and bacterial products such as lipopolysaccharide (LPS), DNA, cell wall antigens and metabolites.  We previously showed the existence of liver autoreactive T cells and associated liver inflammation however, whether the gut contributes to or exacerbates the inflammation in the liver is currently unknown. We are currently using several different approaches to examine whether the gut indeed contributes to the to the liver inflammation in mice depleted of mTECs, through the recruitment of immune cells and/or bacterial products and how this may affect AIH development. We are also examining whether the production of autoreactive effector T cells and reduction of T regulatory cells in the absence of mTECs may affect the gut microbiota and whether peripheral regulatory mechanisms may compensate for these defects.

Gut summary