title: Hepatitis mouse models: from acute-to-chronic autoimmune hepatitis.
abstract: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, raised plasma liver enzymes, the presence of autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is heterogeneous, manifested by a fulminant or indolent course. Although genetic predisposition is well accepted, the combination with currently undefined environmental factors is crucial for the development of the disease. Progress in the development of reliable animal models provides added understanding of the pathophysiology of AIH, and these will be very useful in evaluating potential therapeutics. It appears that artificially breaking tolerance in the liver is easy. However, maintaining this state of tolerance breakdown, to get chronic hepatitis, is difficult because liver immune homeostasis is strongly regulated by several immune response inhibitory mechanisms. For example, Tregs are crucial regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens (CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s), leading to experimental AIH, are likely to be most representative of human AIH pathology.
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium; Department of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Yüksel
authors.forename: Debby
authors.initials: D
authors.lastname: Laukens
authors.forename: Femke
authors.initials: F
authors.lastname: Heindryckx
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.forename: Anja
authors.initials: A
authors.lastname: Geerts
authors.forename: F Susan
authors.initials: FS
authors.lastname: Wong
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
keywords: CYP2D6; Th17; formiminotransferase cyclodeaminase; liver tolerance; mouse models; tregs
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2010 Aug;30(4):443-6
references.pmid: 20714867
references.citation: J Immunol. 2001 May 15;166(10):6413-22
references.pmid: 11342667
references.citation: Liver Int. 2014 Mar;34(3):405-15
references.pmid: 23826746
references.citation: J Autoimmun. 2011 Nov;37(3):242-53
references.pmid: 21795021
references.citation: J Mol Signal. 2013 Jun 13;8(1):7
references.pmid: 23758787
references.citation: J Autoimmun. 2013 Aug;44:49-60
references.pmid: 23809878
references.citation: Eur J Immunol. 2000 Jul;30(7):1919-28
references.pmid: 10940881
references.citation: Q J Med. 1971 Apr;40(158):159-85
references.pmid: 4933363
references.citation: Dig Dis. 2010;28(1):70-9
references.pmid: 20460893
references.citation: Hepatol Res. 2014 Dec;44(13):1299-307
references.pmid: 24506172
references.citation: Autoimmun Rev. 2005 Jul;4(6):373-9
references.pmid: 16081028
references.citation: Immunology. 2011 May;133(1):21-8
references.pmid: 21320121
references.citation: Hepatology. 2013 Jan;57(1):217-27
references.pmid: 22911361
references.citation: Hepatology. 2013 Aug;58(2):718-28
references.pmid: 23475565
references.citation: Clin Exp Immunol. 1987 Feb;67(2):326-34
references.pmid: 3496995
references.citation: Immunity. 2007 Oct;27(4):647-59
references.pmid: 17919941
references.citation: Clin Immunol. 2010 Apr;135(1):156-66
references.pmid: 20080065
references.citation: Hepatology. 2004 Apr;39(4):1066-74
references.pmid: 15057911
references.citation: J Exp Med. 2008 Jun 9;205(6):1409-22
references.pmid: 18474629
references.citation: Gastroenterology. 1996 Aug;111(2):462-71
references.pmid: 8690213
references.citation: Hepatol Int. 2010 May 19;4(2):475-93
references.pmid: 20827405
references.citation: Clin Exp Immunol. 1983 Apr;52(1):89-97
references.pmid: 6305543
references.citation: Nat Rev Immunol. 2012 Dec;12(12):845-57
references.pmid: 23154222
references.citation: Clin Exp Immunol. 1975 Oct;22(1):22-9
references.pmid: 174854
references.citation: Immunol Cell Biol. 2012 Apr;90(4):421-8
references.pmid: 21691280
references.citation: Eur J Immunol. 2008 Apr;38(4):957-67
references.pmid: 18383043
references.citation: Hepatology. 2014 Mar;59(3):1007-15
references.pmid: 23787765
references.citation: Hepatology. 1990 Jan;11(1):24-30
references.pmid: 2271015
references.citation: Ochsner J. 2013 Spring;13(1):131-9
references.pmid: 23531878
references.citation: Hepatology. 2011 Sep 2;54(3):931-9
references.pmid: 21674554
references.citation: J Autoimmun. 2006 Mar;26(2):82-9
references.pmid: 16380229
references.citation: J Immunol. 2013 Jan 15;190(2):526-30
references.pmid: 23248264
references.citation: Sci Rep. 2013 Nov 22;3:3243
references.pmid: 24263861
references.citation: J Clin Pathol. 1994 Dec;47(12):1112-5
references.pmid: 7876386
references.citation: Gastroenterology. 2008 Oct;135(4):1333-43
references.pmid: 18651994
references.citation: J Clin Invest. 2006 Sep;116(9):2456-63
references.pmid: 16955143
references.citation: Hepatology. 2007 Oct;46(4):1155-65
references.pmid: 17657820
references.citation: Gastroenterology. 2013 Jul;145(1):209-220.e9
references.pmid: 23523671
references.citation: Clin Exp Immunol. 1984 Jul;57(1):85-92
references.pmid: 6430615
references.citation: J Autoimmun. 2010 Feb;34(1):7-14
references.pmid: 19766456
references.citation: J Autoimmun. 2008 Nov;31(3):208-15
references.pmid: 18513923
references.citation: Best Pract Res Clin Gastroenterol. 2011 Dec;25(6):783-95
references.pmid: 22117642
references.citation: Hepatol Res. 2012 Feb;42(2):131-8
references.pmid: 22044759
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G525-35
references.pmid: 12466145
references.citation: Hepatology. 2002 Mar;35(3):658-64
references.pmid: 11870381
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16735-40
references.pmid: 21933957
references.citation: J Immunol. 1990 Feb 15;144(4):1187-95
references.pmid: 2303705
references.citation: Eur J Immunol. 1998 Aug;28(8):2395-406
references.pmid: 9710217
references.citation: J Immunol. 2001 May 1;166(9):5430-8
references.pmid: 11313380
references.citation: J Immunol. 2008 Dec 1;181(11):7473-9
references.pmid: 19017936
references.citation: Clin Liver Dis. 2010 Nov;14(4):577-90
references.pmid: 21055683
references.citation: Drug Metab Rev. 2005;37(1):235-52
references.pmid: 15747502
references.citation: World J Gastroenterol. 2009 Mar 7;15(9):1035-41
references.pmid: 19266594
references.citation: Hepatology. 2010 Jun;51(6):2193-213
references.pmid: 20513004
references.citation: Proc Natl Acad Sci U S A. 1989 May;86(10):3782-6
references.pmid: 2657728
references.citation: Gastroenterology. 2010 Jul;139(1):58-72.e4
references.pmid: 20451521
references.citation: Mol Cell Proteomics. 2012 Dec;11(12):1885-97
references.pmid: 22997428
references.citation: Eur J Immunol. 2002 Dec;32(12):3628-37
references.pmid: 12516551
references.citation: J Clin Invest. 2013 Aug;123(8):3510-24
references.pmid: 23867620
references.citation: Hepatology. 2010 Jun;51(6):2040-8
references.pmid: 20512992
references.citation: Immunol Rev. 2000 Apr;174:21-34
references.pmid: 10807504
references.citation: Nat Med. 2005 Feb;11(2):138-45
references.pmid: 15654326
references.citation: Hepatology. 1996 Oct;24(4):824-9
references.pmid: 8855184
references.citation: J Immunol. 2013 Aug 15;191(4):1614-24
references.pmid: 23858031
references.citation: Int Immunol. 2010 Aug;22(8):661-70
references.pmid: 20547544
references.citation: Clin Immunol. 2005 Dec;117(3):280-93
references.pmid: 16246626
references.citation: Exp Anim. 2008 Jan;57(1):45-55
references.pmid: 18256518
references.citation: Am J Pathol. 2010 Nov;177(5):2334-46
references.pmid: 20847291
references.citation: Lancet. 2000 Apr 29;355(9214):1510-5
references.pmid: 10801173
references.citation: Gastroenterology. 2009 Dec;137(6):2125-35.e1-2
references.pmid: 19686746
references.citation: J Biophys Biochem Cytol. 1959 Dec;6:513-4
references.pmid: 14445795
references.citation: Clin Exp Immunol. 1987 Jan;67(1):105-13
references.pmid: 3621670
references.citation: Clin Liver Dis. 2002 Aug;6(3):727-37
references.pmid: 12362577
references.citation: J Immunol. 2002 Sep 1;169(5):2407-13
references.pmid: 12193708
references.citation: J Clin Gastroenterol. 2010 Mar;44(3):208-13
references.pmid: 20087196
references.citation: Int Arch Allergy Appl Immunol. 1968;34(4):345-61
references.pmid: 4301044
references.citation: Scand J Immunol. 2009 Nov;70(5):439-46
references.pmid: 19874548
references.citation: J Hepatol. 2013 Jan;58(1):112-8
references.pmid: 22989568
references.citation: J Clin Invest. 1992 Jul;90(1):196-203
references.pmid: 1634608
references.citation: Hepatology. 1995 Jan;21(1):190-8
references.pmid: 7806154
references.citation: J Virol. 1996 Oct;70(10):7056-61
references.pmid: 8794350
references.citation: Dig Dis Sci. 1995 Feb;40(2):435-56
references.pmid: 7851212
references.citation: Hepatology. 2010 Sep;52(3):999-1007
references.pmid: 20683931
references.citation: Gastroenterology. 2008 Sep;135(3):989-97
references.pmid: 18619445
references.citation: J Exp Med. 2009 Mar 16;206(3):561-76
references.pmid: 19221396
references.citation: Acta Gastroenterol Belg. 1997 Apr-Jun;60(2):176-9
references.pmid: 9260332
references.citation: Br J Haematol. 1956 Jul;2(3):283-94
references.pmid: 13342362
references.citation: Science. 1990 Apr 20;248(4953):361-4
references.pmid: 1691527
references.citation: Gastroenterology. 2010 Sep;139(3):975-86, 986.e1-3
references.pmid: 20639127
references.citation: Novartis Found Symp. 1998;215:159-67; discussion 167-71, 186-90
references.pmid: 9760578
references.citation: J Hepatol. 1994 Nov;21(5):816-21
references.pmid: 7534321
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5498-503
references.pmid: 10792025
references.citation: Immunol Res. 2006;36(1-3):189-95
references.pmid: 17337779
references.citation: J Immunol. 2006 Apr 1;176(7):4484-91
references.pmid: 16547287
references.citation: PLoS One. 2011 Apr 19;6(4):e18909
references.pmid: 21526159
references.citation: J Immunol. 2002 Nov 1;169(9):4889-96
references.pmid: 12391200
references.citation: Nat Immunol. 2010 Jun;11(6):535-42
references.pmid: 20453843
references.citation: Hepatology. 2014 Jan;59(1):354
references.pmid: 23729222
references.citation: Nat Med. 2000 Dec;6(12):1348-54
references.pmid: 11100119
references.citation: J Immunol. 2009 Mar 1;182(5):3278-84
references.pmid: 19234226
references.citation: Hepatology. 2004 Nov;40(5):1211-21
references.pmid: 15486937
references.citation: Hepatology. 2012 Aug;56(2):677-86
references.pmid: 22371007
references.citation: Springerplus. 2013 Jul 30;2:355
references.pmid: 23961418
references.citation: Gastroenterology. 1983 Mar;84(3):596-603
references.pmid: 6218007