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Myeloid cell-like transcript 2 is related to liver inflammation and the pathogenesis of hepatitis B via the involvement of CD8+T cell activation

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Abstract

This study analysed the biological significance of TLT-2 on CD8+T cells in hepatitis B patients and provided a theoretical basis for the potential role of TLT-2 as an immune regulator. Flow cytometry sorting, isobaric tags for relative and absolute quantitation and short hairpin RNAs were used to analyse the function of TLT-2 on CD8+T cells in hepatitis B patients. The TLT-2 expression levels in the acute hepatitis B and chronic hepatitis B groups were significantly higher than that in the healthy control group and were positively correlated with ALT and AST. The CD8+TLT-2+T cells exhibited stronger immune function and greater cell proliferation ability and secreted higher levels of cytokines than the CD8+TLT-2−T cells. An analysis of the proteome differences between the TLT-2+CD8+T and TLT-2−CD8+T cells revealed that TLT-2 affected CD8+T cell activation by regulating Granzyme B expression and by further action on the NF-κB signalling pathway. This study first elucidated the mechanism by which TLT-2 influences the activation of CD8+T cells, improved the understanding of the TLT-2 signalling pathway and clarified the role of the TLT-2+CD8+T cell subset in hepatitis B virus infection. The study proposed a novel subset of CD8+T cells that could be useful for understanding the immune function of patients with hepatitis B and further elucidating the pathogenesis of hepatitis B by analysing changes in this subpopulation with the goal of providing a new target for the treatment of hepatitis B.

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Abbreviations

HBV:

Hepatitis B virus

TREM:

Triggering receptors expressed by myeloid cells

TLT-2:

Trem (triggering receptor expressed on myeloid cells)-like transcript 2

HC:

Healthy controls

AHB:

Acute hepatitis B

CHB:

Chronic hepatitis B

HBV-LC:

Hepatitis B virus-associated liver cirrhosis

HBV-HCC:

Hepatitis B virus-associated hepatocellular carcinoma

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

TBIL:

Total bilirubin

ALB:

Albumi

α-TNF:

Tumor necrosis factor α

CT:

Computed tomography

MRI:

Magnetic resonance imaging

HBeAg:

Hepatitis B e-antigen

PBMCs:

Peripheral blood mononuclear cells

SSC:

Side scatter

FSC:

Forward scatter

iTRAQ:

Isobaric tags for relative and absolute quantitation

LC–MS/MS:

Liquid chromatography coupled to tandem mass spectrometry

GO:

Gene ontology

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NFAT:

Nuclear factor of activated T cells

AP-1:

Activator protein 1

PMA:

Phorbol-12-myristate-13-acetate

BID:

BH3 interacting-domain death agonist

ns:

Not significant

shRNA:

Short hairpin RNA

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Acknowledgements

We thank all patients, clinicians and support staff who participated in this study.

Funding

This work was supported by Grants from the Science and Technology Plan of Suzhou, China (SYS201369 and SS201657), and the Health Plan of Jiangsu, China (H201652 and H2017068).

Author information

Author notes

  1. Jun-Chi Xu, Fei Gao and Yi-An Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatology, The Fifth People’s Hospital of Suzhou, 10, Guangqian Road, Suzhou, 215000, Jiangsu Province, People’s Republic of China

    Jun-Chi Xu, Yi-An Liu, Hui Chen, Xiao-Yan Zhu, Hua-Feng Song, Feng Qian, Ming Li, Chuan-Wu Zhu & Ping Xu

  2. Key Laboratory of Infection and Immunity of Suzhou City, Suzhou, People’s Republic of China

    Jun-Chi Xu, Yi-An Liu, Hui Chen, Xiao-Yan Zhu, Hua-Feng Song, Chuan-Wu Zhu & Ping Xu

  3. The Affiliated Infectious Disease Hospital of Soochow University, Suzhou, People’s Republic of China

    Jun-Chi Xu, Hui Chen, Xiao-Yan Zhu, Hua-Feng Song, Feng Qian, Ming Li, Chuan-Wu Zhu & Ping Xu

  4. The Affiliated Suzhou Hospital of Nanjing Medical University, 26 Daoqian Road, Suzhou, 215000, Jiangsu Province, People’s Republic of China

    Fei Gao & Chen Yang

  5. Suzhou Municipal Hospital, Suzhou, People’s Republic of China

    Fei Gao & Chen Yang

  6. Suzhou Center for Disease Prevention and Control, Suzhou, People’s Republic of China

    Xiao-Long Zhang

Authors
  1. Jun-Chi Xu
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  2. Fei Gao
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  3. Yi-An Liu
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  4. Xiao-Long Zhang
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  7. Hua-Feng Song
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  8. Feng Qian
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  9. Ming Li
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  10. Chen Yang
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  11. Chuan-Wu Zhu
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Corresponding authors

Correspondence to Chen Yang, Chuan-Wu Zhu or Ping Xu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Xu, JC., Gao, F., Liu, YA. et al. Myeloid cell-like transcript 2 is related to liver inflammation and the pathogenesis of hepatitis B via the involvement of CD8+T cell activation. Clin Exp Med 19, 93–104 (2019). https://doi.org/10.1007/s10238-018-0534-1

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  • DOI: https://doi.org/10.1007/s10238-018-0534-1

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