Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease

Cells

Marie Noelle Hilleret¹  Theophile Gerster¹  Vincent Leroy¹  Patrice N. Marche²  Charlotte Costentin²  Marion Mercey-Ressejac²  Zuzana Macek Jilkova²  Jean-Pierre Zarski²  Nathalie Sturm²  Thomas Decaens² 

[1] Service d’Hépato-Gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38700 La Tronche, France;Université Grenoble Alpes, 38000 Grenoble, France;

关键词: autoimmune liver disease;    autoimmune hepatitis;    immune checkpoint molecules;    PD-1;    4-1BB;   

DOI  :  10.3390/cells10102671

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown