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Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner

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Title
Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner
Author(s)
Koh, June-Young; Rha, Min-Seok; Choi, Seong Jin; Lee, Ha Seok; Han, Ji Won; Nam, Heejin; Kim, Dong-Uk; Lee, Jae Geun; Kim, Myoung Soo; Park, Jun Yong; Park, Su-Hyung; Joo, Dong Jin; Eui-Cheol Shin
Publication Date
2022-10
Journal
Journal of Hepatology, v.77, no.4, pp.1059 - 1070
Publisher
Elsevier B.V.
Abstract
Background & Aims: The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated. Methods: We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45+ cells in combination with T cell receptor (TCR)-seq and flow cytometry to examine the phenotypes and functions of liver sinusoidal CD8+ T cells. Results: We identified a distinct CD56hiCD161-CD8+ T-cell population characterized by natural killer (NK)-related gene expression and a uniquely restricted TCR repertoire. The frequency of these cells among the liver sinusoidal CD8+ T-cell population was significantly increased in patients with HBV-associated CLD. Although CD56hiCD161-CD8+ T cells exhibit weak responsiveness to TCR stimulation, CD56hiCD161-CD8+ T cells highly expressed various NK receptors, including CD94, killer immunoglobulin-like receptors, and NKG2C, and exerted NKG2C-mediated NK-like effector functions even in the absence of TCR stimulation. In addition, CD56hiCD161-CD8+ T cells highly respond to innate cytokines, such as IL-12/18 and IL-15, in the absence of TCR stimulation. We validated the results from liver sinusoidal CD8+ T cells using intrahepatic CD8+ T cells obtained from liver tissues. Conclusions: In summary, the current study found a distinct CD56hiCD161-CD8+ T-cell population characterized by NK-like activation via TCR-independent NKG2C ligation. Further studies are required to elucidate the roles of liver sinusoidal CD56hiCD161-CD8+ T cells in immune responses to microbial pathogens or liver immunopathology. Lay summary: The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells – a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance.
URI
https://pr.ibs.re.kr/handle/8788114/12831
DOI
10.1016/j.jhep.2022.05.020
ISSN
0168-8278
Appears in Collections:
Korea Virus Research Institute(한국바이러스기초연구소) > Center for Viral Immunology(바이러스 면역 연구센터) > 1. Journal Papers (저널논문)
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