Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which can affect T cell differentiation and plays a role in various immune diseases. This study mainly explores the role and mechanism of AhR in the immune response after liver transplantation (LT) in rats.

The LT rat models of syngeneic tolerance and allogeneic rejection were established, and the expression levels of AhR and PD-1 in each group were detected at 1, 3, 7 and 14 days after LT. Then the LT rejection models were divided into four groups with different treatments (i.p.). Group A, 1 ml CMC-Na; Group B, 200 mg·kg^-1·d^-1 3,4-DAA; Group C, 10 mg·kg^-1·d^-1 CH223191; Group D, 200 mg·kg^-1·d^-1 3,4-DAA and 10 mg·kg^-1·d^-1 CH223191. After 7 days, the peripheral blood of the recipients was collected to detect liver function and the percentage of CD4⁺Foxp3⁺T cells and CD4⁺PD-1⁺T cells. The liver of recipient rats was collected for pathological examination, and the rejection activity index (RAI) was evaluated by Banff. The changes of AhR and PD-1 in liver tissues were detected by Western blotting and qPCR.

The expression levels of AhR and PD-1 decreased gradually in the LT rejection model, while increased gradually in LT tolerance model. Compared with group A, RAI was decreased, survival time was prolonged and graft rejection was alleviated in group B. In group C, liver function index was significantly up-regulated, RAI was increased, and LT rejection was aggravated. There was no significant difference between group D and group A. The expression of AhR, PD-1, the percentage of CD4⁺Foxp3⁺T cells and CD4⁺PD-1⁺T cells were the same trend in recipient liver.

The expression of AhR and PD-1 decreased with the aggravation of LT rejection, and vice versa. Moreover, AhR activation can effectively reduce the occurrence of acute rejection in rats by increasing the proportion of Treg and the expression of PD-1, which suggests that AhR may be a new target for rejection therapy after LT.