Emerging roles of myeloid derived suppressor cells in hepatic inflammation and fibrosis

Abstract

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune cells that are potent suppressors of immune responses. MDSC emerge in various compartments in the body, such as blood, bone marrow or spleen, especially in conditions of cancer, infections or inflammation. MDSC usually express CD11b, CD33, and low levels of human leukocyte antigen-DR in humans or CD11b and Gr1 (Ly6C/G) in mice, and they can be further divided into granulocytic or monocytic MDSC. The liver is an important organ for MDSC induction and accumulation in hepatic as well as extrahepatic diseases. Different hepatic cells, especially hepatic stellate cells, as well as liver-derived soluble factors, including hepatocyte growth factor and acute phase proteins (SAA, KC), can promote the differentiation of MDSC from myeloid cells. Importantly, hepatic myeloid cells like neutrophils, monocytes and macrophages fulfill essential roles in acute and chronic liver diseases. Recent data from patients with liver diseases and animal models linked MDSC to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma (HCC). In settings of acute hepatitis, MDSC can limit immunogenic T cell responses and subsequent tissue injury. In patients with chronic hepatitis C, MDSC increase and may favor viral persistence. Animal models of chronic liver injury, however, have not yet conclusively clarified the involvement of MDSC for hepatic fibrosis. In human HCC and mouse models of liver cancer, MDSC are induced in the tumor environment and suppress anti-tumoral immune responses. Thus, the liver is a primary site of MDSC in vivo, and modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.

Keywords: Myeloid derived suppressor cells, Interleukin-10, Treg, Liver cirrhosis, Macrophage, Hepatitis C virus

Core tip: Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immune-suppressive cells with important roles during inflammation, infection and cancer. The liver is a primary site for MDSC induction and accumulation, and recent studies linked these cells to the pathogenesis of hepatic inflammation, fibrosis and hepatocellular carcinoma. MDSC can limit tissue injury during acute hepatitis, while they may favor viral persistence in chronic hepatitis. MDSC are also induced during development of liver cancer and suppress anti-tumoral immunity, but their involvement in hepatic fibrosis is less clear. Thus, modulating MDSC functionality might represent a promising novel therapeutic target for liver diseases.