Intrahepatic recruitment of cytotoxic NK cells contributes to autoimmune hepatitis progression

•Peripheral CD56dimNK were decreased in AIH patients at active phase.•Hepatic accumulation of NK cells in experimental autoimmune hepatitis mice along with liver inflammation.•The infiltrated NK cells were mostly conventional CXCR3-cytotoxic NK cells.•CXCR3-NK cells were activated with enhanced degranulation and cytokine production.•Liver resident NK cells were also activated but maintained steady population. Autoimmune hepatitis (AIH) is a chronic autoimmune disease with the primary focus on autoreactive Th1-mediated response and cytotoxic T cells reaction. The contribution of natural killer cells (NK cells) to AIH remains poorly understood. In this project, we revealed that the frequency of peripheral NK cells, more accurately CD56dimNK subset, was reduced in AIH patients. The reduction of CD56dimNK was negatively correlated with disease progression. In experimental autoimmune hepatitis (EAH), hepatic accumulation of NK cells is observed along with a decrease of NK cells in the periphery. In addition, infiltrated NK cells are almost conventional CXCR3− NK cells, the counterpart of CD56dimNK cells in the human. Furthermore, conventional CXCR3-NK cells of infiltration and liver resident NK cells are activated progressively at active phase. Therefore, recruitment of cytotoxic NK cells into the liver, but not liver resident NK cells expansion, may partly account for AIH progression.