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Epigenetics of Primary Biliary Cholangitis

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Epigenetics in Allergy and Autoimmunity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1253))

Abstract

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with non-suppurative destruction of the intrahepatic bile ducts. The interplay of genetics and environmental triggers contributes to the onset of the disease and subsequently results in cholestasis and progressive fibrosis. Recently, genome-wide association studies (GWAS) have identified multiple genes influencing the susceptibility to PBC in HLA and non-HLA loci. However, it is estimated that the known risk variants merely account for no more than 20% of the heritability of PBC and causes of the remaining heritability remain uncertain. Increasing evidence suggests that the presence of epigenetic abnormalities may explain the “missing heritability” that cannot be captured by GWAS. Among these epigenetic mechanisms, DNA methylation, histone modification, and noncoding RNAs (i.e. miRNA and lncRNA) are involved in the pathogenesis of PBC. Additionally, telomere dysregulation in biliary epithelial cells (BECs) may play a role in disease onset, whereas a deficiency in sex chromosome and skewed gene expression in the X chromosome may to some extent explain the female dominance in PBC.

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References

  • Ala A et al (2006) Increased prevalence of primary biliary cirrhosis near Superfund toxic waste sites. Hepatology 43(3):525–531

    Article  PubMed  Google Scholar 

  • Alvarez-Nava F, Lanes R (2018) Epigenetics in turner syndrome. Clin Epigenetics 10:45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Amaral PP et al (2011) lncRNAdb: a reference database for long noncoding RNAs. Nucleic Acids Res 39(Database issue):D146–D151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ananthanarayanan M et al (2015) Post-translational regulation of the type III inositol 1,4,5-trisphosphate receptor by miRNA-506. J Biol Chem 290(1):184–196

    Article  CAS  PubMed  Google Scholar 

  • Ando Y et al (2013) Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-beta receptor type II mouse. J Autoimmun 41:111–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arnold M et al (2012) Cis-acting polymorphisms affect complex traits through modifications of microRNA regulation pathways. PLoS One 7(5):e36694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bae HR et al (2016) Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance. Hepatology 64(4):1189–1201

    Article  CAS  PubMed  Google Scholar 

  • Banales JM et al (2012) Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology 56(2):687–697

    Article  CAS  PubMed  Google Scholar 

  • Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beuers U, Gershwin ME (2015) Unmet challenges in immune-mediated hepatobiliary diseases. Clin Rev Allergy Immunol 48(2–3):127–131

    Article  CAS  PubMed  Google Scholar 

  • Bogdanos DP, Vergani D (2009) Bacteria and primary biliary cirrhosis. Clin Rev Allergy Immunol 36(1):30–39

    Article  PubMed  Google Scholar 

  • Brooks WH et al (2010) Epigenetics and autoimmunity. J Autoimmun 34(3):J207–J219

    Article  CAS  PubMed  Google Scholar 

  • Carbone M et al (2014) Implications of genome-wide association studies in novel therapeutics in primary biliary cirrhosis. Eur J Immunol 44(4):945–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carpenter S et al (2013) A long noncoding RNA mediates both activation and repression of immune response genes. Science 341(6147):789–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cawthon RM et al (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361(9355):393–395

    Article  CAS  PubMed  Google Scholar 

  • Cech TR, Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157(1):77–94

    Article  CAS  PubMed  Google Scholar 

  • Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10(5):295–304

    Article  CAS  PubMed  Google Scholar 

  • Chadha S et al (2005) Haplotype structure of TNFRSF5-TNFSF5 (CD40-CD40L) and association analysis in systemic lupus erythematosus. Eur J Hum Genet 13(5):669–676

    Article  CAS  PubMed  Google Scholar 

  • Cheung AC et al (2017) Epigenetics in the primary biliary cholangitis and primary sclerosing cholangitis. Semin Liver Dis 37(2):159–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Concepcion AR et al (2013) Role of AE2 for pHi regulation in biliary epithelial cells. Front Physiol 4:413

    PubMed  Google Scholar 

  • Cordell HJ et al (2015) International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nat Commun 6:8019

    Article  CAS  PubMed  Google Scholar 

  • Corpechot C et al (2010) Demographic, lifestyle, medical and familial factors associated with primary biliary cirrhosis. J Hepatol 53(1):162–169

    Article  PubMed  Google Scholar 

  • Corpechot C et al (2018) A placebo-controlled trial of bezafibrate in primary biliary cholangitis. N Engl J Med 378(23):2171–2181

    Article  CAS  PubMed  Google Scholar 

  • Dai R, Ahmed SA (2011) MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res 157(4):163–179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong M et al (2015) Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population. Clin Rev Allergy Immunol 48(2–3):316–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du Q et al (2015) Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics 7(6):1051–1073

    Article  CAS  PubMed  Google Scholar 

  • EASL Clinical Practice Guidelines (2017) The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 67(1):145–172

    Article  Google Scholar 

  • Engreitz JM et al (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341(6147):1237973

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Erice O et al (2018) MicroRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation. Hepatology 67(4):1420–1440

    Article  CAS  PubMed  Google Scholar 

  • Euskirchen GM et al (2011) Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches. PLoS Genet 7(3):e1002008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feinberg AP (2018) The key role of epigenetics in human disease prevention and mitigation. N Engl J Med 378(14):1323–1334

    Article  CAS  PubMed  Google Scholar 

  • Gaszner M, Felsenfeld G (2006) Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 7(9):703–713

    Article  CAS  PubMed  Google Scholar 

  • Groom JR, Luster AD (2011) CXCR3 in T cell function. Exp Cell Res 317(5):620–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Groom JR et al (2012) CXCR3 chemokine receptor-ligand interactions in the lymph node optimize CD4+ T helper 1 cell differentiation. Immunity 37(6):1091–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grundmann M et al (2018) Lack of beta-arrestin signaling in the absence of active G proteins. Nat Commun 9(1):341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gulamhusein AF, Juran BD, Lazaridis KN (2015) Genome-wide association studies in primary biliary cirrhosis. Semin Liver Dis 35(4):392–401

    Article  PubMed  PubMed Central  Google Scholar 

  • Guttenbach M et al (1995) Sex chromosome loss and aging: in situ hybridization studies on human interphase nuclei. Am J Hum Genet 57(5):1143–1150

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guttman M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hancock WW et al (2012) HDAC inhibitor therapy in autoimmunity and transplantation. Ann Rheum Dis 71(Suppl 2):i46–i54

    Article  CAS  PubMed  Google Scholar 

  • Heyn H, Esteller M (2012) DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet 13(10):679–692

    Article  CAS  PubMed  Google Scholar 

  • Higuchi M et al (1998) Analysis of CD40 ligand gene mutations in patients with primary biliary cirrhosis. Scand J Clin Lab Invest 58(5):429–432

    Article  CAS  PubMed  Google Scholar 

  • Hirschfield GM, Gershwin ME (2013) The immunobiology and pathophysiology of primary biliary cirrhosis. Annu Rev Pathol 8:303–330

    Article  CAS  PubMed  Google Scholar 

  • Hirschfield GM et al (2018) The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 67(9):1568–1594

    Article  CAS  PubMed  Google Scholar 

  • Hirschfield GM et al (2009) Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med 360(24):2544–2555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirschfield GM et al (2010) Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat Genet 42(8):655–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holoch D, Moazed D (2015) RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet 16(2):71–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horiuchi M et al (2009) Expression and function of histone deacetylases in rheumatoid arthritis synovial fibroblasts. J Rheumatol 36(8):1580–1589

    Article  CAS  PubMed  Google Scholar 

  • Hrdlickova B et al (2014) Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity. Genome Med 6(10):88

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hu N et al (2008) Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol 35(5):804–810

    CAS  PubMed  Google Scholar 

  • Hu Z et al (2011) beta-Arrestin 1 modulates functions of autoimmune T cells from primary biliary cirrhosis patients. J Clin Immunol 31(3):346–355

    Article  CAS  PubMed  Google Scholar 

  • Illingworth RS, Bird AP (2009) CpG islands—‘a rough guide’. FEBS Lett 583(11):1713–1720

    Article  CAS  PubMed  Google Scholar 

  • Invernizzi P et al (2004) Frequency of monosomy X in women with primary biliary cirrhosis. Lancet 363(9408):533–535

    Article  PubMed  Google Scholar 

  • Invernizzi P et al (2014) Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. Dig Liver Dis 46(4):363–368

    Article  CAS  PubMed  Google Scholar 

  • Johnson AD et al (2008) Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. Pharmacogenet Genomics 18(9):781–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13(7):484–492

    Article  CAS  PubMed  Google Scholar 

  • Joshita S et al (2018) Genetics and epigenetics in the pathogenesis of primary biliary cholangitis. Clin J Gastroenterol 11(1):11–18

    Article  PubMed  Google Scholar 

  • Juran BD, Lazaridis KN (2014) Environmental factors in primary biliary cirrhosis. Semin Liver Dis 34(3):265–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juran BD et al (2012) Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants. Hum Mol Genet 21(23):5209–5221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan MM, Gershwin ME (2005) Primary biliary cirrhosis. N Engl J Med 353(12):1261–1273

    Article  CAS  PubMed  Google Scholar 

  • Katsumi T et al (2016) MiR-139-5p is associated with inflammatory regulation through c-FOS suppression, and contributes to the progression of primary biliary cholangitis. Lab Invest 96(11):1165–1177

    Article  CAS  PubMed  Google Scholar 

  • Katsushima F et al (2014) Expression of micro-RNAs in peripheral blood mononuclear cells from primary biliary cirrhosis patients. Hepatol Res 44(10):E189–E197

    Article  CAS  PubMed  Google Scholar 

  • Kawashima M et al (2017) Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. Hum Mol Genet 26(3):650–659

    CAS  PubMed  Google Scholar 

  • Kikuchi K et al (2005) Bacterial CpG induces hyper-IgM production in CD27(+) memory B cells in primary biliary cirrhosis. Gastroenterology 128(2):304–312

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Mahato RI (2015) Delivery and targeting of miRNAs for treating liver fibrosis. Pharm Res 32(2):341–361

    Article  CAS  PubMed  Google Scholar 

  • Lan RY et al (2006) Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology 43(4):729–737

    Article  PubMed  Google Scholar 

  • Lanzi G et al (2010) Different molecular behavior of CD40 mutants causing hyper-IgM syndrome. Blood 116(26):5867–5874

    Article  CAS  PubMed  Google Scholar 

  • Lee JT (2012) Epigenetic regulation by long noncoding RNAs. Science 338(6113):1435–1439

    Article  CAS  PubMed  Google Scholar 

  • Li J et al (2013) miR-122 regulates collagen production via targeting hepatic stellate cells and suppressing P4HA1 expression. J Hepatol 58(3):522–528

    Article  CAS  PubMed  Google Scholar 

  • Liang Y et al (2008) Characterisation of TNF-related apoptosis-inducing ligand in peripheral blood in patients with primary biliary cirrhosis. Clin Exp Med 8(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Liang DY et al (2016) Altered expression of miR-92a correlates with Th17 cell frequency in patients with primary biliary cirrhosis. Int J Mol Med 38(1):131–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X et al (2010) Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 42(8):658–660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu JZ et al (2012) Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat Genet 44(10):1137–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lleo A et al (2009) Apotopes and the biliary specificity of primary biliary cirrhosis. Hepatology 49(3):871–879

    Article  CAS  PubMed  Google Scholar 

  • Lleo A et al (2012) Immunoglobulin M levels inversely correlate with CD40 ligand promoter methylation in patients with primary biliary cirrhosis. Hepatology 55(1):153–160

    Article  CAS  PubMed  Google Scholar 

  • Lleo A et al (2013) Y chromosome loss in male patients with primary biliary cirrhosis. J Autoimmun 41:87–91

    Article  PubMed  Google Scholar 

  • Lleo A et al (2015) DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. Clin Epigenetics 7:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lleo A et al (2017) Primary biliary cholangitis: a comprehensive overview. Hepatol Int 11(6):485–499

    Article  PubMed  Google Scholar 

  • Lu Q (2013) The critical importance of epigenetics in autoimmunity. J Autoimmun 41:1–5

    Article  PubMed  CAS  Google Scholar 

  • Mackay F, Kalled SL (2002) TNF ligands and receptors in autoimmunity: an update. Curr Opin Immunol 14(6):783–790

    Article  CAS  PubMed  Google Scholar 

  • Mao TK et al (2005) Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis. Hepatology 42(4):802–808

    Article  CAS  PubMed  Google Scholar 

  • Marzorati S et al (2016) The epigenetics of PBC: the link between genetic susceptibility and environment. Clin Res Hepatol Gastroenterol 40(6):650–659

    Article  CAS  PubMed  Google Scholar 

  • Mason AL (2011) The evidence supports a viral aetiology for primary biliary cirrhosis. J Hepatol 54(6):1312–1314

    Article  PubMed  Google Scholar 

  • Mayo MJ et al (2006) The relationship between hepatic immunoglobulin production and CD154 expression in chronic liver diseases. Liver Int 26(2):187–196

    Article  CAS  PubMed  Google Scholar 

  • Meda F et al (2011) The epigenetics of autoimmunity. Cell Mol Immunol 8(3):226–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mells GF, Kaser A, Karlsen TH (2013) Novel insights into autoimmune liver diseases provided by genome-wide association studies. J Autoimmun 46:41–54

    Article  CAS  PubMed  Google Scholar 

  • Mells GF et al (2011) Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 43(4):329–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miozzo M et al (2007) Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis. Hepatology 46(2):456–462

    Article  CAS  PubMed  Google Scholar 

  • Mitchell MM et al (2011) Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis. Epigenetics 6(1):95–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Myers RP et al (2009) Epidemiology and natural history of primary biliary cirrhosis in a Canadian health region: a population-based study. Hepatology 50(6):1884–1892

    Article  PubMed  Google Scholar 

  • Nakagawa R et al (2017) miR-425 regulates inflammatory cytokine production in CD4(+) T cells via N-Ras upregulation in primary biliary cholangitis. J Hepatol 66(6):1223–1230

    Article  CAS  PubMed  Google Scholar 

  • Nakamura M (2012) Analysis of disease-pathway by identifying susceptible genes to primary biliary cirrhosis. Nihon Rinsho Meneki Gakkai Kaishi 35(6):503–510

    Article  PubMed  Google Scholar 

  • Nakamura M et al (2012) Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. Am J Hum Genet 91(4):721–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nevens F et al (2016) A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med 375(7):631–643

    Article  CAS  PubMed  Google Scholar 

  • Ninomiya M et al (2013) Distinct microRNAs expression profile in primary biliary cirrhosis and evaluation of miR 505-3p and miR197-3p as novel biomarkers. PLoS One 8(6):e66086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Padgett KA et al (2009) Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J Autoimmun 32(3–4):246–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pang KC et al (2009) Genome-wide identification of long noncoding RNAs in CD8+ T cells. J Immunol 182(12):7738–7748

    Article  CAS  PubMed  Google Scholar 

  • Pelli N et al (2007) Soluble apoptosis molecules in primary biliary cirrhosis: analysis and commitment of the Fas and tumour necrosis factor-related apoptosis-inducing ligand systems in comparison with chronic hepatitis C. Clin Exp Immunol 148(1):85–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poupon R (2010) Primary biliary cirrhosis: a 2010 update. J Hepatol 52(5):745–758

    Article  PubMed  Google Scholar 

  • Qian C et al (2012) MicroRNA profiling in T cells of peripheral blood mononuclear cell from patients with primary biliary cirrhosis. Zhonghua Yi Xue Za Zhi 92(32):2265–2267

    CAS  PubMed  Google Scholar 

  • Qin B et al (2013) Analysis of altered microRNA expression profiles in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. J Gastroenterol Hepatol 28(3):543–550

    Article  CAS  PubMed  Google Scholar 

  • Qiu F et al (2017) A genome-wide association study identifies six novel risk loci for primary biliary cholangitis. Nat Commun 8:14828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakyan VK et al (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet 12(8):529–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rautiainen H et al (2005) Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Hepatology 41(4):747–752

    Article  CAS  PubMed  Google Scholar 

  • Reik W, Lewis A (2005) Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 6(5):403–410

    Article  CAS  PubMed  Google Scholar 

  • Ricano-Ponce I, Wijmenga C (2013) Mapping of immune-mediated disease genes. Annu Rev Genomics Hum Genet 14:325–353

    Article  CAS  PubMed  Google Scholar 

  • Rivera CM, Ren B (2013) Mapping human epigenomes. Cell 155(1):39–55

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto T et al (2016) Identification of microRNA profiles associated with refractory primary biliary cirrhosis. Mol Med Rep 14(4):3350–3356

    Article  CAS  PubMed  Google Scholar 

  • Sasaki M et al (2008) Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence. Hepatology 48(1):186–195

    Article  PubMed  Google Scholar 

  • Schubeler D (2015) Function and information content of DNA methylation. Nature 517(7534):321–326

    Article  CAS  PubMed  Google Scholar 

  • Selmi C et al (2004) Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. Gastroenterology 127(2):485–492

    Article  PubMed  Google Scholar 

  • Selmi C et al (2009) Innate immunity and primary biliary cirrhosis. Curr Mol Med 9(1):45–51

    Article  CAS  PubMed  Google Scholar 

  • Selmi C et al (2014) Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis. Front Immunol 5:128

    PubMed  PubMed Central  Google Scholar 

  • Shay JW (2017) Telomeres and aging. Curr Opin Cell Biol 52:1–7

    Article  PubMed  CAS  Google Scholar 

  • Shimoda S et al (2006) Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory. Gastroenterology 131(2):606–618

    Article  CAS  PubMed  Google Scholar 

  • Shimoda S et al (2010) CX3CL1 (fractalkine): a signpost for biliary inflammation in primary biliary cirrhosis. Hepatology 51(2):567–575

    Article  CAS  PubMed  Google Scholar 

  • Sigdel KR et al (2015) The emerging functions of long noncoding RNA in immune cells: autoimmune diseases. J Immunol Res 2015:848790

    Article  PubMed  PubMed Central  Google Scholar 

  • Sobinoff AP, Pickett HA (2017) Alternative lengthening of telomeres: DNA repair pathways converge. Trends Genet 33(12):921–932

    Article  CAS  PubMed  Google Scholar 

  • Syu BJ et al (2016) Dual roles of IFN-gamma and IL-4 in the natural history of murine autoimmune cholangitis: IL-30 and implications for precision medicine. Sci Rep 6:34884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan Y et al (2014) Serum microRNAs as potential biomarkers of primary biliary cirrhosis. PLoS One 9(10):e111424

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tanaka S et al (2018) KAP1 regulates regulatory T cell function and proliferation in both Foxp3-dependent and independent manners. Cell Rep 23(3):796–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang R et al (2016) A common variant in CLDN14 is associated with primary biliary cirrhosis and bone mineral density. Sci Rep 6:19877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang R et al (2018) Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. Gut 67(3):534–541

    Article  CAS  PubMed  Google Scholar 

  • Trauner M, Halilbasic E (2011) Nuclear receptors as new perspective for the management of liver diseases. Gastroenterology 140(4):1120–1125.e1–12

    Article  CAS  Google Scholar 

  • Tsuda M et al (2011) Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis. Hepatology 54(4):1293–1302

    Article  CAS  PubMed  Google Scholar 

  • Ullah I, Mahajan L, Magnuson D (2017) A newly recognized association of hirschsprung disease with Cri-du-chat syndrome. Am J Gastroenterol 112(1):185–186

    Article  PubMed  Google Scholar 

  • Venkatesh S, Workman JL (2015) Histone exchange, chromatin structure and the regulation of transcription. Nat Rev Mol Cell Biol 16(3):178–189

    Article  CAS  PubMed  Google Scholar 

  • Wang J et al (2001) The regulation of T cell homeostasis and autoimmunity by T cell-derived LIGHT. J Clin Invest 108(12):1771–1780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X et al (2017) MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients. PLoS One 12(9):e0184292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21(6):354–361

    Article  CAS  PubMed  Google Scholar 

  • Webb GJ, Siminovitch KA, Hirschfield GM (2015) The immunogenetics of primary biliary cirrhosis: a comprehensive review. J Autoimmun 64:42–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willeit P et al (2010) Telomere length and risk of incident cancer and cancer mortality. JAMA 304(1):69–75

    Article  CAS  PubMed  Google Scholar 

  • Wu GC et al (2015) Emerging role of long noncoding RNAs in autoimmune diseases. Autoimmun Rev 14(9):798–805

    Article  CAS  PubMed  Google Scholar 

  • Xiao C et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9(4):405–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie YQ, Ma HD, Lian ZX (2016) Epigenetics and primary biliary cirrhosis: a comprehensive review and implications for autoimmunity. Clin Rev Allergy Immunol 50(3):390–403

    Article  CAS  PubMed  Google Scholar 

  • Yang CY et al (2014) IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis: implications for therapy. Hepatology 59(5):1944–1953

    Article  CAS  PubMed  Google Scholar 

  • Yates LA, Norbury CJ, Gilbert RJ (2013) The long and short of microRNA. Cell 153(3):516–519

    Article  CAS  PubMed  Google Scholar 

  • Yikang L, Ma X, Tang R (2017) Advances in genetic research on primary biliary cholangitis. J Clin Hepatol 11:2105–2111

    Google Scholar 

  • Zhang P, Lu Q (2018) Genetic and epigenetic influences on the loss of tolerance in autoimmunity. Cell Mol Immunol 15(6):575–585

    Article  CAS  Google Scholar 

  • Zhang L et al (2013a) Increased expression of lncRNA AK053349 in peripheral blood mononuclear cells from patients with primary biliary cirrhosis and its clinical significance. Int J Lab Med 20(34):2656–2659

    Google Scholar 

  • Zhang Y et al (2013b) Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus. J Autoimmun 41:92–99

    Article  PubMed  CAS  Google Scholar 

  • Zhang H et al (2015) Geoepidemiology, genetic and environmental risk factors for PBC. Dig Dis 33(Suppl 2):94–101

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, 200001, China

    Yikang Li & Ruqi Tang

  2. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China

    Xiong Ma

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  1. Yikang Li
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  2. Ruqi Tang
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  3. Xiong Ma
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Correspondence to Xiong Ma .

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Editors and Affiliations

  1. Division of Pediatric Immunology and Allergy, Joe DiMaggio Children’s Hospital, Hollywood, FL, USA

    Christopher Chang

  2. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Qianjin Lu

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© 2020 Springer Nature Singapore Pte Ltd.

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Li, Y., Tang, R., Ma, X. (2020). Epigenetics of Primary Biliary Cholangitis. In: Chang, C., Lu, Q. (eds) Epigenetics in Allergy and Autoimmunity. Advances in Experimental Medicine and Biology, vol 1253. Springer, Singapore. https://doi.org/10.1007/978-981-15-3449-2_10

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