{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:02:00Z","timestamp":1781521320952,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds Agir pour les Maladies Chroniques","award":["2020"],"award-info":[{"award-number":["2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis (AIH). Here, we performed a multiparametric analysis of ICM, including PD-1, TIM3, LAG3, CTLA-4, OX40 and 4-1BB, and we determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with AIH in comparison to normal liver tissue. AIH patient-derived liver tissue revealed the overexpression of ICM, mainly PD-1 and 4-1BB, as well as the strong correlation between PD-1+ CD8+ T-cell abundance and severity of AIH (alanine transaminase and aspartate transaminase levels). Our results show that the ICM play an important role in the loss of immune homeostasis in the liver, providing an attractive approach to investigate their role as targets for effective therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cells10102671","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"2671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2553-5971","authenticated-orcid":false,"given":"Zuzana","family":"Macek Jilkova","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"},{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"},{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults (FILFOIE), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Noelle","family":"Hilleret","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"},{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults (FILFOIE), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theophile","family":"Gerster","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"},{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults (FILFOIE), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Sturm","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Service d\u2019Anatomo-Pathologie, P\u00f4le de Biologie, CHU Grenoble Alpes, 38700 La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Mercey-Ressejac","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"},{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Zarski","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"},{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Leroy","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-9340","authenticated-orcid":false,"given":"Patrice N.","family":"Marche","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Costentin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"},{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"},{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults (FILFOIE), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0928-0048","authenticated-orcid":false,"given":"Thomas","family":"Decaens","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, 38000 Grenoble, France"},{"name":"Research Center Inserm U1209, Institute for Advanced Biosciences, CNRS UMR5309, 38700 La Tronche, France"},{"name":"Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, P\u00f4le Digidune, CHU Grenoble Alpes, 38700 La Tronche, France"},{"name":"Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), French Network for Rare Liver Diseases in Children and Adults (FILFOIE), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jhep.2013.09.020","article-title":"Autoimmune liver disease, autoimmunity and liver transplantation","volume":"60","author":"Carbone","year":"2014","journal-title":"J. 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