Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change

Abstract

Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.

Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis

“…Zhang et al (2017) further confirmed that IL-17A inhibits hepatocyte autophagy through the IL-10/STAT3 signaling Frontiers in Molecular Biosciences frontiersin.org pathway and plays a pivotal role in the pathogenesis of LF. Moreover, natural killer, natural killer T, memory B, and central memory CD4 T cells have been demonstrated to be involved in the occurrence and development of LF (Wang and Yin, 2015;Huang et al, 2020;Zuluaga et al, 2020;Zuluaga et al, 2022). Therefore, our results were consistent with these previous reports, and our bioinformatics analysis further emphasized the important role of these immune cells in the pathogenesis of LF.…”

Cytotoxic NK cells phenotype and activated lymphocytes are the main characteristics of patients with alcohol-associated liver disease

“…The results of this study suggest that AUD patients with advanced liver fibrosis have more cytotoxic CD56 + CD16 + NK cells, fewer cytokine-secreting CD56 + CD16 − NK cells and an increased lymphocyte activation, defined by HLA-DR expression, than patients without advanced liver fibrosis. Our group previously described the increase in the absolute counts of NK cells and cytotoxic T cells subsets in patients with advanced fibrosis, but these results expand the description of the phenotype of NK [ 26 ].…”

Gut-microbiota prompt activation of natural killer cell on alcoholic liver disease

“…Considering that NK cells constitute the dominant lymphocyte population in the liver and that alcohol can suppress these NK cells 55 , we conducted an experiment to determine the changes in NK cells caused by probiotic strains in ALD. There were no significant differences in NK cell frequency or cytotoxicity in mice with ethanol-induced liver disease.…”