Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury.

Abstract

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.

• Authors: Estefanía Caballano-Infantes, Alberto García-García, Carlos Lopez-Gomez, Alejandro Cueto, Mercedes Robles-Diaz, Aida Ortega-Alonso, Flores Martín-Reyes, Ismael Alvarez-Alvarez, Isabel Arranz-Salas, Francisco Ruiz-Cabello, Isabel M Lucena, Eduardo García-Fuentes, Raúl J Andrade, Miren García-Cortes
• Journal: Biomedicines (Biomedicines) Vol. 10 Issue 1 (Dec 28 2021) ISSN: 2227-9059 [Print] Switzerland
• PMID: 35052736 (Publication Type: Journal Article)