{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:06:08Z","timestamp":1779512768717,"version":"3.53.1"},"reference-count":116,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Current Opinion in Immunology"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.coi.2026.102786","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:52:27Z","timestamp":1778817147000},"page":"102786","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Can we cure primary biliary cholangitis?"],"prefix":"10.1016","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-8087","authenticated-orcid":false,"given":"Palak J","family":"Trivedi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M","family":"Hirschfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Eric Gershwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.coi.2026.102786_bib1","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1136\/gutjnl-2020-322362","article-title":"Recent advances in clinical practice: epidemiology of autoimmune liver diseases","volume":"70","author":"Trivedi","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.coi.2026.102786_bib2","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0140-6736(20)31607-X","article-title":"Primary biliary cholangitis","volume":"396","author":"Lleo","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.coi.2026.102786_bib3","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0140-6736(24)01303-5","article-title":"Primary biliary cholangitis","volume":"404","author":"Tanaka","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.coi.2026.102786_bib4","unstructured":"NHSBT Organ specific reports; Liver. ODT Clin - NHS Blood Transpl n.d. \u3008https:\/\/nhsbtdbe.blob.core.windows.net\/umbraco-assets-corp\/37114\/nhsbt-liver-transplantation-report-2425.pdf\u3009 (accessed October 23, 2025)."},{"key":"10.1016\/j.coi.2026.102786_sbref4","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/hep.22736","article-title":"Apotopes and the biliary specificity of primary biliary cirrhosis","volume":"49","author":"Lleo","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib6","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","article-title":"Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study","volume":"147","author":"Lammers","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib7","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1053\/j.gastro.2024.01.049","article-title":"Immunopathogenesis of primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis: themes and concepts","volume":"166","author":"Trivedi","year":"2024","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib8","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/cei.12224","article-title":"Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrial antibodies in non-obese diabetic (NOD).B6 (Idd10\/Idd18) mice","volume":"175","author":"Wang","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.coi.2026.102786_sbref8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/hep.32172","article-title":"E. coli and the etiology of human PBC: antimitochondrial antibodies and spreading determinants","volume":"75","author":"Yang","year":"2022","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib10","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jaut.2005.01.012","article-title":"Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis","volume":"24","author":"Padgett","year":"2005","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib11","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1053\/jhep.2003.50446","article-title":"Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium","volume":"38","author":"Selmi","year":"2003","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib12","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1002\/hep.26157","article-title":"Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary biliary cirrhosis","volume":"57","author":"Chen","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib13","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/art.41994","article-title":"Antibody responses to Epstein-Barr virus in the preclinical period of rheumatoid arthritis suggest the presence of increased viral reactivation cycles","volume":"74","author":"Fechtner","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.coi.2026.102786_bib14","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1038\/s41591-025-03692-w","article-title":"T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis","volume":"31","author":"ElAbd","year":"2025","journal-title":"Nat Med"},{"key":"10.1016\/j.coi.2026.102786_bib15","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"10.1016\/j.coi.2026.102786_bib16","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00296-012-2504-3","article-title":"EBV reactivation serological profile in primary Sj\u00f6gren\u2019s syndrome: an underlying trigger of active articular involvement?","volume":"33","author":"Pasoto","year":"2013","journal-title":"Rheumatol Int"},{"key":"10.1016\/j.coi.2026.102786_bib17","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-53104-9","article-title":"Single-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis","volume":"15","author":"Jin","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.coi.2026.102786_bib18","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1096\/fj.01-0088com","article-title":"CD40 activation-induced, Fas-dependent apoptosis and NF-kappaB\/AP-1 signaling in human intrahepatic biliary epithelial cells","volume":"15","author":"Afford","year":"2001","journal-title":"FASEB J"},{"key":"10.1016\/j.coi.2026.102786_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.898615","article-title":"Animal models for autoimmune hepatitis: are current models good enough?","volume":"13","author":"Christen","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.jtauto.2023.100189","article-title":"Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis - a case series","volume":"6","author":"Kolev","year":"2023","journal-title":"J Transl Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib21","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/HEP.0000000000000557","article-title":"Osteopontin characterizes bile duct-associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis","volume":"79","author":"De Muynck","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ng.627","article-title":"Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis","volume":"42","author":"Liu","year":"2010","journal-title":"Nat Genet"},{"key":"10.1016\/j.coi.2026.102786_bib23","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jaut.2005.08.009","article-title":"Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives","volume":"25","author":"Chuang","year":"2005","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib24","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.jhep.2012.07.008","article-title":"CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver","volume":"57","author":"Oo","year":"2012","journal-title":"J Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib25","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/hep4.1170","article-title":"NI-0801, an anti-chemokine (C-X-C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid","volume":"2","author":"de Graaf","year":"2018","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.coi.2026.102786_bib26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jaut.2016.12.012","article-title":"Chemokine receptor CXCR3 deficiency exacerbates murine autoimmune cholangitis by promoting pathogenic CD8+ T cell activation","volume":"78","author":"Ma","year":"2017","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib27","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/hep.24526","article-title":"Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis","volume":"54","author":"Tsuda","year":"2011","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2025.103806","article-title":"Role of regulatory T cells in inflammatory liver diseases","volume":"24","author":"Yang","year":"2025","journal-title":"Autoimmun Rev"},{"key":"10.1016\/j.coi.2026.102786_bib29","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jaut.2018.07.020","article-title":"Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-\u03b3 secreting cells","volume":"94","author":"Liaskou","year":"2018","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib30","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/hep.29782","article-title":"MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation","volume":"68","author":"B\u00f6ttcher","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib31","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-025-56363-2","article-title":"Single cell profiling of circulating autoreactive CD4 T cells from patients with autoimmune liver diseases suggests tissue imprinting","volume":"16","author":"Cardon","year":"2025","journal-title":"Nat Commun"},{"key":"10.1016\/j.coi.2026.102786_bib32","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s41586-020-2396-4","article-title":"A metabolic pathway for bile acid dehydroxylation by the gut microbiome","volume":"582","author":"Funabashi","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.coi.2026.102786_sbref32","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41586-022-04480-z","article-title":"Human gut bacteria produce \u03a4\u039717-modulating bile acid metabolites","volume":"603","author":"Paik","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.coi.2026.102786_sbref33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","article-title":"Microbial bile acid metabolites modulate gut ROR\u03b3+ regulatory T cell homeostasis","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.coi.2026.102786_sbref34","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41586-020-2193-0","article-title":"Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells","volume":"581","author":"Campbell","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.coi.2026.102786_bib36","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2023.2208501","article-title":"Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis","volume":"15","author":"Martinez-Gili","year":"2023","journal-title":"Gut Microbes"},{"key":"10.1016\/j.coi.2026.102786_sbref36","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/hep.25691","article-title":"Up-regulation of microRNA 506 leads to decreased Cl-\/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis","volume":"56","author":"Banales","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_sbref37","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/hep.29533","article-title":"MicroRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation","volume":"67","author":"Erice","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib39","article-title":"Histone\/protein deacetylase 11 targeting promotes Foxp3+ Treg function","volume":"7","author":"Huang","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.coi.2026.102786_bib40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1053\/j.gastro.2020.10.008","article-title":"Epigenomic evaluation of cholangiocyte transforming growth factor-\u03b2 Signaling identifies a selective role for histone 3 lysine 9 acetylation in biliary fibrosis","volume":"160","author":"Aseem","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib41","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/hep.27959","article-title":"Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin-1","volume":"62","author":"Barbier-Torres","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib42","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1053\/j.gastro.2024.05.014","article-title":"Gut microbiota-derived butyrate induces epigenetic and metabolic reprogramming in myeloid-derived suppressor cells to alleviate primary biliary cholangitis","volume":"167","author":"Wang","year":"2024","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jaut.2012.12.008","article-title":"Y chromosome loss in male patients with primary biliary cirrhosis","volume":"41","author":"Lleo","year":"2013","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib44","doi-asserted-by":"crossref","DOI":"10.1186\/s13148-015-0098-9","article-title":"DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis","volume":"7","author":"Lleo","year":"2015","journal-title":"Clin Epigenetics"},{"key":"10.1016\/j.coi.2026.102786_bib45","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/hep.21696","article-title":"Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis","volume":"46","author":"Miozzo","year":"2007","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib46","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1053\/j.gastro.2021.02.061","article-title":"X chromosome contribution to the genetic architecture of primary biliary cholangitis","volume":"160","author":"Asselta","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib47","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jhep.2018.08.020","article-title":"Primary biliary cholangitis: a tale of epigenetically-induced secretory failure?","volume":"69","author":"Rodrigues","year":"2018","journal-title":"J Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib48","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/ajg.2017.440","article-title":"Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: risk factors and time trends in incidence and outcome","volume":"113","author":"Harms","year":"2018","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.coi.2026.102786_sbref48","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMoa2312100","article-title":"A phase 3 trial of seladelpar in primary biliary cholangitis","volume":"390","author":"Hirschfield","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.coi.2026.102786_sbref49","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa2306185","article-title":"Efficacy and safety of elafibranor in primary biliary cholangitis","volume":"390","author":"Kowdley","year":"2024","journal-title":"N Engl J Med"},{"key":"10.1016\/j.coi.2026.102786_sbref50","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N Engl J Med"},{"key":"10.1016\/j.coi.2026.102786_sbref51","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1056\/NEJMoa1714519","article-title":"A placebo-controlled trial of bezafibrate in primary biliary cholangitis","volume":"378","author":"Corpechot","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.coi.2026.102786_bib53","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/ncpgasthep0521","article-title":"Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis","volume":"3","author":"Beuers","year":"2006","journal-title":"Nat Clin Pract Gastroenterol Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib54","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1478-3231.2007.01506.x","article-title":"Expression of bile acid synthesis and detoxification enzymes and the alternative bile acid efflux pump MRP4 in patients with primary biliary cirrhosis","volume":"27","author":"Zollner","year":"2007","journal-title":"Liver Int"},{"key":"10.1016\/j.coi.2026.102786_bib55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1586\/17512433.2015.1092381","article-title":"Obeticholic acid for the treatment of primary biliary cirrhosis","volume":"9","author":"Trivedi","year":"2016","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.coi.2026.102786_bib56","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0092-8674(00)00062-3","article-title":"Targeted disruption of the nuclear receptor fxr\/bar impairs bile acid and lipid homeostasis","volume":"102","author":"Sinal","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.coi.2026.102786_bib57","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/s42255-021-00452-1","article-title":"Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling","volume":"3","author":"Schneider","year":"2021","journal-title":"Nat Metab"},{"key":"10.1016\/j.coi.2026.102786_bib58","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.4049\/jimmunol.0901347","article-title":"The bile acid sensor farnesoid X receptor is a modulator of liver immunity in a rodent model of acute hepatitis","volume":"183","author":"Mencarelli","year":"2009","journal-title":"J Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib59","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jhep.2021.04.010","article-title":"Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis","volume":"75","author":"Tanaka","year":"2021","journal-title":"J Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib60","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/apt.70378","article-title":"Non-response to obeticholic acid is associated with heightened risks of developing clinical events in primary biliary cholangitis","volume":"63","author":"Abbas","year":"2026","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.coi.2026.102786_bib61","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ueg2.12095","article-title":"Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease","volume":"9","author":"Cortez-Pinto","year":"2021","journal-title":"United European Gastroenterol J"},{"key":"10.1016\/j.coi.2026.102786_bib62","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.cgh.2018.12.028","article-title":"Effects of age and sex of response to ursodeoxycholic acid and transplant-free survival in patients with primary biliary cholangitis","volume":"17","author":"Cheung","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib63","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1053\/j.gastro.2012.12.005","article-title":"Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid","volume":"144","author":"Carbone","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib64","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1002\/hep.32011","article-title":"The serum proteome and ursodeoxycholic acid response in primary biliary cholangitis","volume":"74","author":"Barron-Millar","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib65","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.14309\/ajg.0000000000000557","article-title":"Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase","volume":"115","author":"Murillo Perez","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.coi.2026.102786_bib66","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/HEP.0000000000000529","article-title":"Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: to what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?","volume":"79","author":"Corpechot","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib67","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1053\/j.gastro.2018.10.001","article-title":"Factors associated with recurrence of primary biliary cholangitis after liver transplantation and effects on graft and patient survival","volume":"156","author":"Montano-Loza","year":"2019","journal-title":"Gastroenterology"},{"key":"10.1016\/j.coi.2026.102786_bib68","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/hep.28517","article-title":"Human intrahepatic regulatory T cells are functional, require IL-2 from effector cells for survival, and are susceptible to Fas ligand-mediated apoptosis","volume":"64","author":"Chen","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib69","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1056\/NEJMoa1108188","article-title":"Interleukin-2 and regulatory T cells in graft-versus-host disease","volume":"365","author":"Koreth","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1016\/j.coi.2026.102786_bib70","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2024.103172","article-title":"The universal effects of low-dose interleukin-2 across 13 autoimmune diseases in a basket clinical trial","volume":"144","author":"Lorenzon","year":"2024","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib71","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nm.4148","article-title":"Low-dose interleukin-2 treatment selectively modulates CD4+ T cell subsets in patients with systemic lupus erythematosus","volume":"22","author":"He","year":"2016","journal-title":"Nat Med"},{"key":"10.1016\/j.coi.2026.102786_bib72","article-title":"Low-dose IL-2 reduces IL-21+ T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat Commun"},{"key":"10.1016\/j.coi.2026.102786_sbref72","doi-asserted-by":"crossref","DOI":"10.1172\/JCI173107","article-title":"A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models","volume":"134","author":"Efe","year":"2024","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_bib74","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aba5264","article-title":"An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice","volume":"5","author":"Khoryati","year":"2020","journal-title":"Sci Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib75","article-title":"Regulatory T cell therapy in autoimmune liver disease and transplantation","volume":"7","author":"Fleming","year":"2025","journal-title":"JHEP Rep"},{"key":"10.1016\/j.coi.2026.102786_bib76","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aaw2707","article-title":"Conversion of antigen-specific effector\/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8\/19","volume":"4","author":"Akamatsu","year":"2019","journal-title":"Sci Immunol"},{"issue":"22","key":"10.1016\/j.coi.2026.102786_bib77","doi-asserted-by":"crossref","first-page":"12258","DOI":"10.1073\/pnas.1922600117","article-title":"Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation","volume":"117","author":"Mikami","year":"2020","journal-title":"PNAS"},{"key":"10.1016\/j.coi.2026.102786_bib78","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2024.103327","article-title":"Identification of a novel PDC-E2 epitope in primary biliary cholangitis: application for engineered Treg therapy","volume":"149","author":"Tewari","year":"2024","journal-title":"J Autoimmun"},{"key":"10.1016\/j.coi.2026.102786_bib79","doi-asserted-by":"crossref","first-page":"384","DOI":"10.2337\/db23-0996","article-title":"Preclinical development of a tolerogenic peptide from glutamate decarboxylase as a candidate for antigen-specific immunotherapy in type 1 diabetes","volume":"74","author":"Ng","year":"2025","journal-title":"Diabetes"},{"key":"10.1016\/j.coi.2026.102786_bib80","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1053\/jhep.2002.36161","article-title":"Comprehensive mapping of HLA-A*0201\u2013restricted CD8 T-cell epitopes on PDC-E2 in primary biliary cirrhosis","volume":"36","author":"Matsumura","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib81","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1172\/JCI0214698","article-title":"Quantitative and functional analysis of PDC-E2\u2013specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis","volume":"109","author":"Kita","year":"2002","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_bib82","first-page":"918","article-title":"Analysis of TCR antagonism and molecular mimicry of an HLA-A0201-restricted CTL epitope in primary biliary cirrhosis","volume":"36","author":"Kita","year":"2002","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib83","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.autrev.2007.02.003","article-title":"Glatiramer acetate: mechanisms of action in multiple sclerosis","volume":"6","author":"Schrempf","year":"2007","journal-title":"Autoimmun Rev"},{"key":"10.1016\/j.coi.2026.102786_bib84","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1084\/jem.189.8.1275","article-title":"Microbial epitopes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis","volume":"189","author":"Ruiz","year":"1999","journal-title":"J Exp Med"},{"key":"10.1016\/j.coi.2026.102786_bib85","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jhep.2015.01.006","article-title":"Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice","volume":"62","author":"Carambia","year":"2015","journal-title":"J Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib86","doi-asserted-by":"crossref","DOI":"10.4254\/wjh.v17.i6.104073","article-title":"Effect of rapamycin nanoparticles in an animal model of primary biliary cholangitis","volume":"17","author":"Yang","year":"2025","journal-title":"World J Hepatol"},{"key":"10.1016\/j.coi.2026.102786_bib87","article-title":"Tolerogenic treatment with CNP-104 results in regulation TH17 cells slowing progression of PBC on liver stiffness","volume":"80","author":"Frey","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.coi.2026.102786_bib88","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2024.122997","article-title":"Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis","volume":"316","author":"Phan","year":"2025","journal-title":"Biomaterials"},{"key":"10.1016\/j.coi.2026.102786_bib89","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1039\/D2BM00444E","article-title":"Dual peptide nanoparticle platform for enhanced antigen-specific immune tolerance for the treatment of experimental autoimmune encephalomyelitis","volume":"10","author":"Wang","year":"2022","journal-title":"Biomater Sci"},{"key":"10.1016\/j.coi.2026.102786_bib90","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1021\/acsbiomaterials.9b00332","article-title":"Dual-sized microparticle system for generating suppressive dendritic cells prevents and reverses type 1 diabetes in the nonobese diabetic mouse model","volume":"5","author":"Lewis","year":"2019","journal-title":"ACS Biomater Sci Eng"},{"key":"10.1016\/j.coi.2026.102786_bib91","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2019.119440","article-title":"Antigen-specific immune decoys intercept and exhaust autoimmunity to prevent disease","volume":"222","author":"Griffin","year":"2019","journal-title":"Biomaterials"},{"key":"10.1016\/j.coi.2026.102786_bib92","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1172\/JCI4213","article-title":"Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis","volume":"102","author":"Shimoda","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_bib93","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1172\/JCI8476","article-title":"MHC class II tetramers identify peptide-specific human CD4(+) T cells proliferating in response to influenza A antigen","volume":"104","author":"Novak","year":"1999","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_bib94","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.2337\/diabetes.51.5.1375","article-title":"Detection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjects","volume":"51","author":"Reijonen","year":"2002","journal-title":"Diabetes"},{"key":"10.1016\/j.coi.2026.102786_bib95","doi-asserted-by":"crossref","first-page":"7735","DOI":"10.1073\/pnas.1406218111","article-title":"Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation","volume":"111","author":"David","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.coi.2026.102786_bib96","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01586","article-title":"Antigen-specific immunotherapy for treatment of autoimmune liver diseases","volume":"11","author":"Richardson","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib97","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nri2132","article-title":"Tolerogenic dendritic cells and the quest for transplant tolerance","volume":"7","author":"Morelli","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib98","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.2337\/dc11-0472","article-title":"Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients","volume":"34","author":"Giannoukakis","year":"2011","journal-title":"Diabetes Care"},{"key":"10.1016\/j.coi.2026.102786_bib99","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1002\/art.27756","article-title":"Therapeutic effect of tolerogenic dendritic cells in established collagen-induced arthritis is associated with a reduction in Th17 responses","volume":"62","author":"Stoop","year":"2010","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.coi.2026.102786_bib100","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1136\/annrheumdis-2015-208456","article-title":"Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis","volume":"76","author":"Bell","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.coi.2026.102786_bib101","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1002\/art.22655","article-title":"Antigen-specific suppression of established arthritis in mice by dendritic cells deficient in NF-kappaB","volume":"56","author":"Martin","year":"2007","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.coi.2026.102786_bib102","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa9301","article-title":"Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients","volume":"7","author":"Benham","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.coi.2026.102786_bib103","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1073\/pnas.1820039116","article-title":"Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial","volume":"116","author":"Zubizarreta","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"10.1016\/j.coi.2026.102786_bib104","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S2213-8587(20)30104-2","article-title":"Safety and feasibility of intradermal injection with tolerogenic dendritic cells pulsed with proinsulin peptide\u2014for type 1 diabetes","volume":"8","author":"Nikolic","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.coi.2026.102786_bib105","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.2217\/nnm-2016-0410","article-title":"Liposome-based immunotherapy against autoimmune diseases: therapeutic effect on multiple sclerosis","volume":"12","author":"Pujol-Autonell","year":"2017","journal-title":"Nanomed"},{"key":"10.1016\/j.coi.2026.102786_bib106","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41586-025-08795-5","article-title":"Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3","volume":"642","author":"Chen","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.coi.2026.102786_bib107","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.4049\/jimmunol.1900848","article-title":"Efficient CRISPR\/Cas9 disruption of autoimmune-associated genes reveals key signaling programs in primary human T cells","volume":"203","author":"Anderson","year":"2019","journal-title":"J Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib108","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-01236-6","article-title":"Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Nat Commun"},{"key":"10.1016\/j.coi.2026.102786_bib109","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1172\/JCI123267","article-title":"Reduced expression of phosphatase PTPN2 promotes pathogenic conversion of Tregs in autoimmunity","volume":"129","author":"Svensson","year":"2019","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_bib110","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.4049\/jimmunol.1700024","article-title":"Genetic and small molecule disruption of the AID\/RAD51 Axis similarly protects nonobese diabetic mice from type 1 diabetes through expansion of regulatory B lymphocytes","volume":"198","author":"Ratiu","year":"2017","journal-title":"J Immunol"},{"key":"10.1016\/j.coi.2026.102786_bib111","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10238-009-0052-2","article-title":"Resistance to activation-induced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:C-induced primary biliary cirrhosis mouse model","volume":"9","author":"Jiang","year":"2009","journal-title":"Clin Exp Med"},{"key":"10.1016\/j.coi.2026.102786_bib112","article-title":"Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.coi.2026.102786_bib113","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1172\/JCI16344","article-title":"Sensitizing antigen-specific CD8+ T cells for accelerated suicide causes immune incompetence","volume":"111","author":"Wasem","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1016\/j.coi.2026.102786_sbref113","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"CD19CAR T-cell therapy in autoimmune disease - a case series with follow-up","volume":"390","author":"M\u00fcller","year":"2024","journal-title":"N Engl J"},{"key":"10.1016\/j.coi.2026.102786_sbref114","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1038\/s41591-022-02017-5","article-title":"Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus","volume":"28","author":"Mackensen","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.coi.2026.102786_bib116","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","article-title":"High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells","volume":"31","author":"Fu","year":"2013","journal-title":"Nat Biotechnol"}],"container-title":["Current Opinion in Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0952791526000634?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0952791526000634?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T04:23:26Z","timestamp":1779510206000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0952791526000634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":116,"alternative-id":["S0952791526000634"],"URL":"https:\/\/doi.org\/10.1016\/j.coi.2026.102786","relation":{},"ISSN":["0952-7915"],"issn-type":[{"value":"0952-7915","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Can we cure primary biliary cholangitis?","name":"articletitle","label":"Article Title"},{"value":"Current Opinion in Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.coi.2026.102786","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102786"}}