Protective and Pathological Properties of IL-22 in Liver Disease

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
American Journal Of Pathology (Impact Factor: 4.59). 11/2012; 182(1). DOI: 10.1016/j.ajpath.2012.08.043
Source: PubMed


Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection affect >500 million people worldwide, and are significant causes of liver cirrhosis and hepatocellular carcinoma. The pathogenesis of HBV and HCV infection can vary widely with respect to the outcome of initial infection to self-resolving acute or chronic disease, the extent of viremia and liver inflammation during chronic infection, and the eventual development of liver cirrhosis and hepatocellular carcinoma. The host immune response is an important factor in the variable consequences of these infections, because the innate and adaptive intrahepatic antiviral responses are an intricate balance of immune effector cells and cytokines that control virus replication but can also cause liver damage. IL-22 is an important cytokine that plays a pleiotropic protective, but sometimes also pathological, role in several tissues/organs, including the liver. Therefore, IL-22 is likely to be an important factor in the pathogenesis and clinical outcome of HBV and HCV infection. However, the precise beneficial, and possible detrimental, effects of this cytokine may vary among different disease states that are associated with distinct inflammatory microenvironments. This review summarizes our understanding of the protective and pathological activities of IL-22, with an emphasis on the liver, and discusses the implications of these effects as they relate to viral hepatitis.

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    • "Current studies demonstrated that CD3+T activated NKT and NK cells, which were the major cell types that produce IL-22 in the HBV-infected livers [49]. IL-22 may play a proinflammatory role during acute HBV infection, perhaps by amplifying immune cell infiltration and clearance of virus, whereas it may play a more protective role during chronic HBV infection [50]. "
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    ABSTRACT: Interleukin (IL)-22, originally referred to as IL-TIF for IL-10-related T cell-derived inducible factor, is a member of the IL-10-like cytokine family. IL-22 is highly expressed by Th17 cells and is tightly linked to chronic inflammation, including inflammatory bowel disease and local intestinal inflammation among others. A PubMed and Web of Science databases search was performed for studies providing evidences on the role of IL-22 in liver diseases. IL-22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL-22 receptor 1 and IL-10 receptor 2. This review concisely summarizes the role of IL-22 in the development progression of liver disease of different etiologies. It is focused mainly on the IL-22 intracellular signaling and its influence on liver diseases.
    Agents and Actions 03/2014; 63(7). DOI:10.1007/s00011-014-0727-3 · 2.35 Impact Factor
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    ABSTRACT: Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we didn't find enhancement of HBsAg-specific antibody responses in comparison to mice immunized with pcD-S2 alone. However, there was an enhancement of the level of IL-17 expression in antigen specific CD8 (+) cytotoxic T lymphocytes (Tc17). By using CD8 T-cell knockout (KO) and IL-17 KO mice, Tc17 cells were found to be a dominant population driving cytotoxicity. Importantly, there was a correlation between pVAX-IL-22 enhancement of T lymphocytes and a reduction of HBsAg-positive hepatocytes in HBsAg transgenic mice. These results demonstrate that IL-22 might be used as an effective adjuvant to enhance cellular immune responses during HBsAg DNA vaccination since it can induce Tc17 cells to break tolerance in HBsAg transgenic mice.
    Human Vaccines & Immunotherapeutics 08/2013; 9(10). DOI:10.4161/hv.26047 · 2.37 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) infection remains a worldwide health problem, and is the major cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma. The innate and adaptive immune responses of the HBV-infected host contribute greatly to the development and pathogenesis of chronic HBV infection, and often affect the efficacy of anti-HBV drugs. Interleukin (IL)-22 is a newly identified cytokine that is involved in the pathogenesis of liver disease, but its role in liver inflammation in patients with HBV infection remains controversial. In this report, we summarize the production and function of IL-22 in inflammatory environments, and review the current research into IL-22 biology in HBV infection. A better understanding of the intrahepatic microenvironments that directly influence the activity of IL-22 will be important for the development of new immunotherapeutic approaches that target IL-22-producing cells or IL-22 itself.
    11/2013; 1(2):103-108. DOI:10.14218/JCTH.2013.00013
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