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Impaired antibacterial response of liver sinusoidal Vγ9 + Vδ2 + T cells in patients with chronic liver disease

Authors
 Min-Seok Rha  ;  Ji Won Han  ;  June-Young Koh  ;  Ha Seok Lee  ;  Jong Hoon Kim  ;  Kyungjoo Cho  ;  Soon Il Kim  ;  Myoung Soo Kim  ;  Jae Geun Lee  ;  Su-Hyung Park  ;  Dong Jin Joo  ;  Jun Yong Park  ;  Eui-Cheol Shin 
Citation
 GUT, Vol.71(3) : 605-615, 2022-03 
Journal Title
GUT
ISSN
 0017-5749 
Issue Date
2022-03
Keywords
bacterial translocation ; chronic liver disease ; gamma-delta cells ; liver immunology
Abstract
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.
Full Text
https://gut.bmj.com/content/71/3/605
DOI
10.1136/gutjnl-2020-322182
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Soon Il(김순일) ORCID logo https://orcid.org/0000-0002-0783-7538
Kim, Jong Hoon(김종훈) ORCID logo https://orcid.org/0000-0002-3385-8180
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Lee, Jae Geun(이재근) ORCID logo https://orcid.org/0000-0002-6722-0257
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188056
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