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Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534248/ https://www.ncbi.nlm.nih.gov/pubmed/34685651 http://dx.doi.org/10.3390/cells10102671 |
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author | Macek Jilkova, Zuzana Hilleret, Marie Noelle Gerster, Theophile Sturm, Nathalie Mercey-Ressejac, Marion Zarski, Jean-Pierre Leroy, Vincent Marche, Patrice N. Costentin, Charlotte Decaens, Thomas |
author_facet | Macek Jilkova, Zuzana Hilleret, Marie Noelle Gerster, Theophile Sturm, Nathalie Mercey-Ressejac, Marion Zarski, Jean-Pierre Leroy, Vincent Marche, Patrice N. Costentin, Charlotte Decaens, Thomas |
author_sort | Macek Jilkova, Zuzana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8534248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85342482021-10-23 Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease Macek Jilkova, Zuzana Hilleret, Marie Noelle Gerster, Theophile Sturm, Nathalie Mercey-Ressejac, Marion Zarski, Jean-Pierre Leroy, Vincent Marche, Patrice N. Costentin, Charlotte Decaens, Thomas Cells Article 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. MDPI 2021-10-06 /pmc/articles/PMC8534248/ /pubmed/34685651 http://dx.doi.org/10.3390/cells10102671 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Macek Jilkova, Zuzana Hilleret, Marie Noelle Gerster, Theophile Sturm, Nathalie Mercey-Ressejac, Marion Zarski, Jean-Pierre Leroy, Vincent Marche, Patrice N. Costentin, Charlotte Decaens, Thomas Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title | Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title_full | Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title_fullStr | Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title_full_unstemmed | Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title_short | Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease |
title_sort | increased intrahepatic expression of immune checkpoint molecules in autoimmune liver disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534248/ https://www.ncbi.nlm.nih.gov/pubmed/34685651 http://dx.doi.org/10.3390/cells10102671 |
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