한빛사 논문
Min-Seok Rha1, Ji Won Han1,2, June-Young Koh1, Ha Seok Lee1, Jong Hoon Kim1,3, Kyungjoo Cho4, Soon Il Kim5, Myoung Soo Kim5, Jae Geun Lee5, Su-Hyung Park1, Dong Jin Joo5,6, Jun Yong Park7, Eui-Cheol Shin1
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
2Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Republic of Korea
3Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
4Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
5Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
6The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
7Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
Correspondence to Professor Eui-Cheol Shin, Professor Jun Yong Park
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.
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