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),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)-γ,tumor necrosis factor (TNF)-a and intedeukin (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.
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