PT  - JOURNAL ARTICLE
AU  - Min-Seok Rha
AU  - Ji Won Han
AU  - June-Young Koh
AU  - Ha Seok Lee
AU  - Jong Hoon Kim
AU  - Kyungjoo Cho
AU  - Soon Il Kim
AU  - Myoung Soo Kim
AU  - Jae Geun Lee
AU  - Su-Hyung Park
AU  - Dong Jin Joo
AU  - Jun Yong Park
AU  - Eui-Cheol Shin
TI  - Impaired antibacterial response of liver sinusoidal Vγ9<sup>+</sup>Vδ2<sup>+</sup> T cells in patients with chronic liver disease
AID  - 10.1136/gutjnl-2020-322182
DP  - 2021 Jan 20
TA  - Gut
PG  - gutjnl-2020-322182
4099  - http://gut.bmj.com/content/early/2021/01/20/gutjnl-2020-322182.short
4100  - http://gut.bmj.com/content/early/2021/01/20/gutjnl-2020-322182.full
AB  - Objective The liver acts as a frontline barrier against diverse gut-derived pathogens, and the sinusoid is the primary site of liver immune surveillance. However, little is known about liver sinusoidal immune cells in the context of chronic liver disease (CLD). Here, we investigated the antibacterial capacity of liver sinusoidal γδ T cells in patients with various CLDs.Design We analysed the frequency, phenotype and functions of human liver sinusoidal γδ T cells from healthy donors and recipients with CLD, including HBV-related CLD (liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC)), alcoholic LC and LC or HCC of other aetiologies, by flow cytometry and RNA-sequencing using liver perfusates obtained during living donor liver transplantation. We also measured the plasma levels of D-lactate and bacterial endotoxin to evaluate bacterial translocation.Results The frequency of liver sinusoidal Vγ9+Vδ2+ T cells was reduced in patients with CLD. Immunophenotypic and transcriptomic analyses revealed that liver sinusoidal Vγ9+Vδ2+ T cells from patients with CLD were persistently activated and pro-apoptotic. In addition, liver sinusoidal Vγ9+Vδ2+ T cells from patients with CLD showed significantly decreased interferon (IFN)-γ production following stimulation with bacterial metabolites and Escherichia coli. The antibacterial IFN-γ response of liver sinusoidal Vγ9+Vδ2+ T cells significantly correlated with liver function, and inversely correlated with the plasma level of D-lactate in patients with CLD. Repetitive in vitro stimulation with E. coli induced activation, apoptosis and functional impairment of liver sinusoidal Vγ9+Vδ2+ T cells.Conclusion Liver sinusoidal Vγ9+Vδ2+ T cells are functionally impaired in patients with CLD. Bacterial translocation and decreasing liver functions are associated with functional impairment of liver sinusoidal Vγ9+Vδ2+ T cells.