摘要
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）, BT-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）-γ, tumor necrosis factor （TNF）-α 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-γ （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-γ （r =0.261, P 〈0.05）. While TNF-α 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-γ and IL-4. PD-1 system may play an important role in the pathogenesis of AIH.
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）, BT-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）-γ, tumor necrosis factor （TNF）-α 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-γ （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-γ （r =0.261, P 〈0.05）. While TNF-α 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-γ and IL-4. PD-1 system may play an important role in the pathogenesis of AIH.
