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10.1002/hep.27998 http://scihub22266oqcxt.onion/10.1002/hep.27998 C4763614!4763614 !26185095     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26185095 &cmd=llinks): Failed to open stream: HTTP request failed! 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A novel "humanized mouse" model for autoimmune hepatitis and the association of gut microbiota with liver inflammation |pdf=|usr=}}{{26185095 }} gab.com Text A novel "humanized mouse" model for autoimmune hepatitis and the association of gut microbiota with liver inflammation JO: Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=26185095 #FOAvip Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease characterized by interface hepatitis, the presence of circulating autoantibodies, and hyper-gammaglobulinemia. There are two types of AIH, type 1 (AIH-1) and type 2 (AIH-2), characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or antinuclear autoantibodies, whereas patients with AIH-2 have anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 autoantibodies. Cytochrome P4502D6 is the antigenic target of anti-liver kidney microsomal type 1, and formiminotransferase cyclodeaminase is the antigenic target of anti-liver cytosol type 1. It is known that AIH, both types 1 and 2, is strongly linked to the human leukocyte antigen (HLA) alleles -DR3, -DR4, and -DR7. However, direct evidence of the association of HLA with AIH is lacking. We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the nonobese-diabetic background by immunization of HLA-DR3- and HLA-DR3+ nonobese-diabetic mice with a DNA plasmid, coding for human cytochrome P4502D6/formiminotransferase cyclodeaminase fusion protein. Immunization with cytochrome P4502D6/formiminotransferase cyclodeaminase leads to a sustained elevation of alanine aminotransferase, development of antinuclear autoantibodies and anti-liver kidney microsomal type 1/anti-liver cytosol type 1 autoantibodies, chronic immune cell infiltration, and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced T helper 1 immune response and paucity of the frequency of regulatory T cells in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. CONCLUSION: Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. Twit Text FOAVip A novel "humanized mouse" model for autoimmune hepatitis and the association of gut microbiota with liver inflammation ????Hepatology http://www.kidney.de/pget.php?&tw=1&pmid=26185095 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26185095 #FOAvip English Wikipedia <ref>{{Cite pmid|26185095 }}</ref> A novel "humanized mouse" model for autoimmune hepatitis and the association of gut microbiota with liver inflammation #MMPMID26185095 Yuksel M ; Wang Y ; Tai N ; Peng J ; Guo J ; Beland K ; Lapierre P ; David C ; Alvarez F ; Colle I ; Yan H ; Mieli-Vergani G ; Vergani D ; Ma Y ; Wen L Hepatology 2015[Nov]; 62 (5 ): 1536-50 PMID26185095 show ga Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease characterized by interface hepatitis, the presence of circulating autoantibodies, and hyper-gammaglobulinemia. There are two types of AIH, type 1 (AIH-1) and type 2 (AIH-2), characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or antinuclear autoantibodies, whereas patients with AIH-2 have anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 autoantibodies. Cytochrome P4502D6 is the antigenic target of anti-liver kidney microsomal type 1, and formiminotransferase cyclodeaminase is the antigenic target of anti-liver cytosol type 1. It is known that AIH, both types 1 and 2, is strongly linked to the human leukocyte antigen (HLA) alleles -DR3, -DR4, and -DR7. However, direct evidence of the association of HLA with AIH is lacking. We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the nonobese-diabetic background by immunization of HLA-DR3- and HLA-DR3+ nonobese-diabetic mice with a DNA plasmid, coding for human cytochrome P4502D6/formiminotransferase cyclodeaminase fusion protein. Immunization with cytochrome P4502D6/formiminotransferase cyclodeaminase leads to a sustained elevation of alanine aminotransferase, development of antinuclear autoantibodies and anti-liver kidney microsomal type 1/anti-liver cytosol type 1 autoantibodies, chronic immune cell infiltration, and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced T helper 1 immune response and paucity of the frequency of regulatory T cells in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. CONCLUSION: Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. |*Microbiota [MESH] |Animals [MESH] |Autoantibodies/immunology [MESH] |Base Sequence [MESH] |Cytochrome P-450 CYP2D6/immunology [MESH] |Cytokines/biosynthesis [MESH] |Disease Models, Animal [MESH] |HLA-DR3 Antigen/immunology [MESH] |Hepatitis, Autoimmune/*etiology [MESH] |Humans [MESH] |Immunization [MESH] |Intestines/*microbiology [MESH] |Liver/pathology [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH] |Mice, Inbred NOD [MESH] |Molecular Sequence Data [MESH]A novel "humanized mouse" model for autoimmune hepatitis and the assoc(epmc).pdf DeepDyve Pubget Overpricing