Abstract Text: Primary biliary cholangitis (PBC) is a chronic autoimmune disease where the immune system attacks the small bile ducts in the liver. CD8 T cells are known to play a significant role in destroying the bile ducts. However, regulatory T cells (Tregs), a type of immune cell that regulates the immune response, have also been found to accumulate in the liver of patients with PBC. This study used a xenobiotic-induced mouse model of PBC-like disease to test the idea that Tregs in PBC are not functioning correctly. In our study, female and male mice treated with 2-octynoic acid-conjugated ovalbumin (2-OA-OVA) developed autoimmune cholangitis (AIC). However, female AIC mice had worse liver inflammation and damage than male mice. Additionally, there were higher levels of CD8 T cells and their chemoattractants, CXCL9 and CXCL10, in the livers of female AIC mice. There were also more Tregs in the livers of mice with the PBC-like disease, but these Tregs did not have normal levels of CTLA-4 and TGF-β that help them control the immune response. Moreover, although treating the mice with low-dose IL-2 increased the number of hepatic Tregs, these Tregs could not rescue the pathology of AIC. Overall, these results suggest that Tregs in PBC were dysfunctional, and transferring with normal Tregs may be a better way to treat PBC.
