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

Table 1 Functional role of myeloid derived suppressor cells in the regulation of human and murine liver diseases

Species	Type of disease	Surface phenotype	Function of MDSC	Mechanism	Ref.
Human	Chronic HCV infection	CD11b+ HLA-DRlo CD33+ CD14+	Inhibition of T cell proliferation and IFNγ production	Arginase1	[6]
Human	HCV-infected hepatocytes	CD11b+/lo HLA-DRlo/- CD33+ CD14+	Inhibition of T cell cytokine production	ROS Cell-cell-contact	[7]
Human	HCC	CD11b+ HLA-DR- CD33+ CD14-	Long-lasting inhibition of effector T cells		[22-30]
Human	HCC	HLA-DRlo/- CD14+	Inhibition of natural killer cells	Cell-cell-contact NKp30	[33]
Human	HCC	HLA-DRlo/- CD14+	Induction of Treg and inhibition of effector T cells	Arginase	[29]
Mouse	CCl4-mediated fibrosis	CD11b+Ly6G-Ly6ChiF4/80+	Amelioration of fibrosis through inhibition of HSC	IL-10 production	[13]
		CD11b+Ly6G+Ly6CloF4/80-
Mouse	Th1-mediated inflammation	CD11b+Ly6G-Ly6Chi	Inhibition of T cell proliferation (CD4+ and CD8+)	iNOS cell-cell-contact	[48]
		CD11b+Ly6G+Ly6Clo
Mouse	Sepsis	CD11b+Gr1+	Inhibition of IL-12 and induction of IL-10 release by macrophages	Cell-cell-contact	[2]
Mouse	Immune-mediated hepatitis	CD11b+Ly6GloLy6Chi	Suppression of CD4+ T cell proliferation	iNOS	[46,47]
		CD11b+Ly6G+Ly6Clo
Mouse	ConA-mediated hepatitis	CD11b+Ly6G-Ly6C+	Protection against liver injury through inhibition of T cells	Arginase	[4]
		CD11b+Ly6G+Ly6C+(int)
Mouse	ConA/LPS-mediated hepatitis	CD11b+Ly6GloLy6Chi	Suppression of CD4+ T cell proliferation and cytokine production	iNOS cell-cell-contact	[3,45]
		CD11b+Ly6GhiLy6Cint
Mouse	CTL-mediated liver injury	CD11b+Gr1+	Suppression of CTL proliferation and IFNγ production		[21]
Mouse	HBV (transgenics)	CD11b+Gr1+	Suppression of HBV-specific CTL	Arginase iNOS	[5]
Mouse	HCC/primary liver tumors	CD11b+Gr1+	Suppression of anti-tumor CTL		[35,36,38]
Mouse	Gastrointestinal cancer with liver metastasis	CD11b+Gr1+/int	Inhibition of T cell proliferation and tumor cell lysis		[40]

ConA: Concanavalin A; CTL: Cytotoxic T lymphocyte; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; IFN: Interferon; IL: Interleukin; iNOS: Inducible nitric oxide synthase; ROS: Reactive oxygen species; Treg: Regulatory T cell; MDSC: Myeloid derived suppressor cells.