Figure 2.

Mechanisms of aberrant Th17-cell immunity in AIH. Expression of CD39 by Th17-cells is associated with acquisition of regulatory properties. These include increased FOXP3 expression levels, IL-10 production and control of effector cell proliferation and function. In healthy subjects, levels of CD39 in Th17-cells are regulated by the aryl-hydrocarbon-receptor (AhR)/aryl-hydrocarbon-receptor-nuclear-translocator (ARNT) complex. In AIH, Th17-cells display decreased CD39 levels and activity. This is linked, at least in part, with high levels of hypoxia-inducible-factor-1alpha (HIF-1α) that inhibits AhR levels and signaling. Th17-cells from AIH patients also display reduced levels of A2A adenosine receptor, this implicating defective response of these cells to the immunosuppressive effects of adenosine.