Expression of programmed death 1 and its ligands in the liver of autoimmune hepatitis C57BL/6 mice.

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with unknown etiology. Programmed death 1 (PD-1) and its ligands (PD-L1 and PD-L2), B7-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that are involved in the regulation of immune responses. Previous observation suggests that PD-1 system plays an inhibitory role in regulating peripheral blood T cells, B cells and myeloid cells, thus their abnormality may be related to autoimmune diseases. This study aimed to explore the role of PD-1/PD-L1, L2 system in the pathogenesis of AIH.

Methods: The mice model of experimental autoimmune hepatitis (EAH) was established in C57BL/6 mice and the expression levels of PD-1 and PD-L1, L2 in the murine liver and the cytokines, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-4 in the spleen were detected using reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with those of normal controls.

Results: The expression levels of PD-1, PD-L1, PD-L2 mRNA were higher in EAH compared with normal controls (P < 0.05), the PD-L2/PD-1 ratio was relatively lower in EAH (EAH -0.08 +/- 0.35, normal controls 0.52 +/- 0.07, P = 0.009). In the EAH, the expression of the three cytokines were all upregulated compared with normal controls. PD-L1 had a positive correlation with the expression of IFN-gamma (r = 0.289, P < 0.05), while PD-L2 showed a positive correlation with both expressions of IL-4 (r = 0.378, P< 0.01) and IFN-gamma (r = 0.261, P < 0.05). While TNF-alpha showed no correlation with PD-L1 (r = 0.044, P = 0.736) or PD-L2 (r = 0.127, P = 0.335).

Conclusions: The expression of PD-1/PD-L1, L2 is upregulated in EAH and regulated by IFN-gamma and IL-4. PD-1 system may play an important role in the pathogenesis of AIH.