AIM: To research the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved. IFN-γ were observed in the hepatic fibrosis group compared with the control group (< 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis which was confirmed by lower hepatic fibrosis pathological scores (< 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% 4-Methylumbelliferone (4-MU) 8.09% ± 0.74% < 0.01) Th17 cells (4.34% ± 0.37% 5.71% ± 0.24% < 0.01) Th1 cells (3.09% ± 0.49% 4.91% ± 0.73% < 0.01) and the levels of IL-22 (56.23 ± 3.08 70.29 ± 3.01 < 0.01) IL-17A (30.74 ± 2.77 45.68 ± 2.71 < 0.01) and IFN-γ (74.78 ± 2.61 124.89 ± 2.82 < 0.01). Down-regulation of IL-22 IL-17A IFN-γ TNF-α IL-6 IL-1β AHR RORγt and T-bet gene expression in the liver was observed in the rmIL-22 group (< 0.01). CONCLUSION: The frequencies of Th22 Th17 and Th1 cells are elevated in 4-Methylumbelliferone (4-MU) hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines thereby ameliorating liver fibrogenesis. attenuation of hepatic stellate cell activation and down-regulation of inflammatory cytokines. INTRODUCTION Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic liver injury. Activation of hepatic stellate cells (HSCs) is considered the most important event in the production of extracellular matrix (ECM) and collagens thereby leading to hepatic fibrosis[1]. Despite advances in the characterization of the fibrotic process the exact molecular mechanisms of the 4-Methylumbelliferone (4-MU) disease are 4-Methylumbelliferone (4-MU) poorly understood. Persistent immunological responses and inappropriate release of immune mediators have been linked to injury damage and scar formation in host tissues and identified as crucial pathological processes. However the fundamental mechanisms responsible for liver fibrosis have not been completely clarified. Recently emerging evidence has shown that CD4+T cells play an important role in the development of liver inflammation and fibrosis[2-4]. CD4+T helper cells have recently been 4-Methylumbelliferone (4-MU) subdivided into four major subsets largely based on their expression profile of transcription factors and secreted cytokines: T helper (Th) cell type 1 Th2 Th17 and regulatory T cells[5 6 Th1 cells are characterized by the secretion of interferon-γ (IFN-γ) a proinflammatory cytokine which is necessary for the activation of macrophages and is involved in immunity against intracellular pathogens. Studies have shown that injection of IFN-γ decreased total liver collagen content in rats with dimethylnitrosamine-induced fibrosis[7]. Nevertheless IFN-γ inhibits HSC proliferation and activation and down-regulates the expression of ECM in these cells. Th17 cells are a more recently discovered subset of CD4+ T-helper cells characterized by the production of their signature cytokine IL-17. They represent another subtype of proinflammatory T-helper cells that differs from Th1 and Th2 cells in development and function. Differentiation of Th17 cells requires the combined actions of transforming growth factor beta (TGF-β) IL-6 and IL-21 in mice. These cytokines induce the expression of the orphan nuclear receptor RAR-related orphan receptor (RORγt) (mice) or RORc (human). Th17 cells have been demonstrated to play a critical role in inflammatory diseases autoimmune diseases and graft-versus-host diseases by secreting IL-17A and other cytokines. Several studies have revealed that Th17 cells are involved in the pathogenesis of liver diseases[8 9 Th22 cells have been recognized as a novel Th cell subset which are characterized by abundant production of IL-22 but not IL-17 or IFN-γ[10 11 Th22 cells express the chemokine receptors CCR6 CCR4 and CCR10 and have high expression of the key transcription factor aryl hydrocarbon receptor (AHR) but low or undetectable expression of T-bet and Spry4 ROR-γt[10]. In addition the differentiation toward the Th22 phenotype from naive T cells occurs in the presence of IL-6 and tumor necrosis factor-α (TNF-α)[10]. Developing literature has demonstrated that Th22 cells are associated with psoriasis rheumatoid arthritis systemic sclerosis and human immunodeficiency virus infection. However the presence of Th22 cells and the role of Th22 in hepatic fibrosis are unknown. IL-22 is a member of the IL-10 cytokine family and is produced primarily by Th22 cells Th17 cells and Th1.