Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury Caballano Infantes, Estefanía Ruiz-Cabello Osuna, Francisco Non-alcoholic fatty liver disease (NAFLD) Drug-induced liver injury (DILI) Immunophenotype Immune response Liver fibrosis This work was supported in part by a grant from the Instituto de Salud Carlos III (Spain) (PI18/01804, PI19/00883, PI21/01248), from the Consejeria de Economia, Conocimiento, Empresas y Universidad (Junta de Andalucia, Spain) (UMA18-FEDERJA-194, PI18-RT-3364), and from the Consejeria de Salud (Junta de Andalucia, Spain) (PI-0285-2016). This study has been co-funded by FEDER funds ("A way to make Europe") ("Andalucia se mueve con Europa"). Background: Non-alcoholic fatty liver disease (NAFLD) and idiosyncratic drug-induced liver injury (DILI) could share molecular mechanisms involving the immune system. We aimed to identify activation immunological biomarkers in invariant natural killer T (iNKT) and CD4/CD8+ T cells in NAFLD and DILI. Methods: We analyzed the activation profile (CD69, CD25, and HLA-DR) and natural killer group 2 member D (NKG2D) on iNKT cells, and CD4/CD8 T cells in peripheral blood mononuclear cells from NAFLD, with or without significant liver fibrosis, and DILI patients. Results: There was an increase in iNKT cells in NAFLD patients compared to DILI or control subjects. Regarding the cellular activation profile, NAFLD with significant liver fibrosis (F >= 2) displayed higher levels of CD69+iNKT cells compared to NAFLD with none or mild liver fibrosis (F <= 1) and control patients. CD69+iNKT positively correlated with insulin resistance, aspartate aminotransferase (AST) level, liver fibrosis-4 index (FIB4) and AST to Platelet Ratio Index (APRI). DILI patients showed an increase in CD69+ and HLA-DR+ in both CD4+ and CD8+ T cells, detecting the most relevant difference in the case of CD69+CD8+ T cells. Conclusions: CD69+iNKT may be a biomarker to assess liver fibrosis progression in NAFLD. CD69+CD8+ T cells were identified as a potential distinctive biomarker for distinguishing DILI from NAFLD. 2022-03-08T07:33:47Z 2022-03-08T07:33:47Z 2021-12-28 info:eu-repo/semantics/article Caballano-Infantes, E... [et al.]. Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury. Biomedicines 2022, 10, 55. [https://doi.org/10.3390/biomedicines10010055] http://hdl.handle.net/10481/73198 10.3390/biomedicines10010055 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI