Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters

Zhipeng Wu; Hongbo Shi; Lei Zhang; Honglin Shi; Xingzhong Miao; Liangjuan Chen; Yu Chen; Yingmin Ma

doi:10.3389/fimmu.2023.1290445

Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters

Front Immunol. 2023 Dec 4:14:1290445. doi: 10.3389/fimmu.2023.1290445. eCollection 2023.

Authors

Zhipeng Wu^#^{1

2}, Hongbo Shi^#^{2

3

4}, Lei Zhang^{5

6}, Honglin Shi^{2

3}, Xingzhong Miao^{2

3}, Liangjuan Chen^{2

3}, Yu Chen⁴, Yingmin Ma^{1

2}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China.
² Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
³ Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer, Beijing, China.
⁴ Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital, Capital Medical University, Beijing, China.
⁵ Department of Nephrology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Shanxi, China.
⁶ Department of Traditional Chinese Medicine, Qinhuangdao Shanhaiguan People's Hospital, Hebei, China.

^# Contributed equally.

Abstract

Background: Acute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated.

Methods: This study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared.

Results: Our study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients' T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production.

Conclusion: ACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.

Keywords: T cell stimulatory function; acute-on-chronic liver failure; clinical parameters; monocyte-derived dendritic cell; phenotype.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute-On-Chronic Liver Failure* / metabolism
Albumins / metabolism
Dendritic Cells
HLA-DR Antigens / metabolism
Humans
Leukocytes, Mononuclear
Monocytes*
Phenotype

Substances

HLA-DR Antigens
Albumins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Beijing Nova Program (Grant No. 20220484201), Beijing Natural Science Foundation (Grant No. M22030) and Beijing municipal medical research institute public welfare development and reform pilot project (Grant No. jingyiyan2021-10).