Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury
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Non-alcoholic fatty liver disease (NAFLD)Drug-induced liver injury (DILI)ImmunophenotypeImmune responseLiver fibrosis
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]
SponsorshipInstituto de Salud Carlos III PI18/01804 PI19/00883 PI21/01248; Junta de Andalucia UMA18-FEDERJA-194 PI18-RT-3364 PI-0285-2016; 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.
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