IL-17A produced by invariant natural killer T cells and CD3 CD56 αGalcer-CD1d tetramer T cells promote liver fibrosis in patients with primary biliary cholangitis.

Primary biliary cholangitis (PBC) is characterized as interlobular bile duct injury and fibrosis, which results from the loss of tolerance to self-antigens. However, the exact pathologic mechanism leading to injury and fibrosis in PBC patients is not fully understood. Therefore, in this study, we examined the role of the T cell subsets in PBC patients and healthy controls (HCs). A higher number of invariant Natual killer T (iNKT) cells as well as CD3 CD56 αGalcer-CD1d tetramer T cells were found in patients with PBC compared with HCs. Moreover, these 2 T subpopulations produced significantly higher levels of Interleukin (IL)-17A in PBC patients than those in in HCs, which has also been positively correlated with the disease severity. Furthermore, the level of IL-17A produced by these 2 subpopulations was increased after stimulation of the autoantibodies in patients with PBC. Also, the elevated IL-17A levels promoted the PBC-related fibrosis, thus presenting a change in frequencies and functions of these cell phenotypes in the deterioration of the duct damage-related fibrosis. This study clarified PBC patients' distinct T subpopulations characteristics, providing evidence-based diagnostic and therapies for these patients. The correlation between unclassical T subsets and IL-17A may provide a novel target for the immunotherapy of PBC.