Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease

Autor: Zuzana Macek Jilkova, Marie Noelle Hilleret, Theophile Gerster, Nathalie Sturm, Marion Mercey-Ressejac, Jean-Pierre Zarski, Vincent Leroy, Patrice N. Marche, Charlotte Costentin, Thomas Decaens
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cells, Vol 10, Iss 10, p 2671 (2021)
Druh dokumentu: article
ISSN: 10102671
2073-4409
DOI: 10.3390/cells10102671
Popis: 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.
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