Dendritic cell-CD8+ T cell communication is essential for Kinsenoside, a potential immunosuppression drug for autoimmune hepatitis

Abstract Autoimmune hepatitis (AIH) is a chronic auto-immune inflammation against liver tissue. Here, using T cell-deficient mice, acute AIH mice model and a novel AIH mice model induced by dendritic cells loaded with murine hepatocellular carcinoma cells (DC/Hepa1–6) vaccination, we reveal that Kinsenoside (KD), a major component of Anoectochilus roxburghii, has an powerful therapeutic effect on AIH by limiting the metabolism of immune cells such as DCs and CD8+ T cells, which results in the immunosuppression against autoimmune liver injury. The immunosuppressive and anti-inflammatory effect of KD is triggered by increased the expression of co-inhibitory molecules PD-L1/PD-1 to inhibit DC cross-priming of CD8+ T cell responses but not modulate the hepatotoxicity of CD8+ T cells directly. Furthermore, KD reduces immune cells metabolism and executes immunosuppressive and anti-inflammatory action by binding to the potential target VEGFR2 and blocking the cross-talk of metabolism related PI3K-AKT and inflammation related JAK2-STAT3 signaling pathways.