https://scholars.lib.ntu.edu.tw/handle/123456789/507613
標題: | AAV-IL-22 modifies liver chemokine activity and ameliorates portal inflammation in murine autoimmune cholangitis | 作者: | Hsueh Y.-H. Chang Y.-N. Loh C.-E. Gershwin M.E. YA-HUI CHUANG |
公開日期: | 2016 | 卷: | 66 | 起(迄)頁: | 89-97 | 來源出版物: | Journal of Autoimmunity | 摘要: | There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC. ? 2015 Elsevier Ltd. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/507613 | ISSN: | 0896-8411 | DOI: | 10.1016/j.jaut.2015.10.005 | SDG/關鍵字: | alpha galactosylceramide; CXCL9 chemokine; gamma interferon inducible protein 10; interleukin 10; interleukin 22; macrophage inflammatory protein 3beta; RANTES; alpha-galactosylceramide; Ccl19 protein, mouse; Ccl5 protein, mouse; Cxcl10 protein, mouse; CXCL9 chemokine; Cxcl9 protein, mouse; galactosylceramide; gamma interferon inducible protein 10; interleukin derivative; interleukin-22; macrophage inflammatory protein 3beta; RANTES; Adeno associated virus; animal experiment; animal model; animal tissue; Article; autoimmune liver disease; cholangitis; controlled study; down regulation; female; liver; liver fibrosis; lymphocytic infiltration; mouse; nonhuman; priority journal; protein blood level; protein expression; regulatory T lymphocyte; Th1 cell; animal; Autoimmune Diseases; biological therapy; C57BL mouse; cholangitis; Dependoparvovirus; disease model; gene vector; genetics; immunology; Liver Cirrhosis, Biliary; metabolism; pathology; portal vein; procedures; vascularization; Animals; Autoimmune Diseases; Biological Therapy; Chemokine CCL19; Chemokine CCL5; Chemokine CXCL10; Chemokine CXCL9; Cholangitis; Dependovirus; Disease Models, Animal; Female; Galactosylceramides; Genetic Vectors; Interleukins; Liver; Liver Cirrhosis, Biliary; Mice; Mice, Inbred C57BL; Portal System |
顯示於: | 醫學檢驗暨生物技術學系 |
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