Imbalance Between Soluble and Membrane-Bound CD100 Regulates Monocytes Activity in Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure

Viral Immunol. 2021 May;34(4):273-283. doi: 10.1089/vim.2020.0311. Epub 2021 Feb 26.


CD100 is an important immune semaphorin that is a secreted and membrane bound protein involved in infectious diseases. However, CD100 expression profile and the regulation to innate immune system in hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) was not previously reported. The aim of this study was to investigate CD100 level and modulatory function of CD100 to CD14+ monocytes in HBV-ACLF patients. Plasma-soluble CD100 (sCD100) level and membrane-bound CD100 (mCD100) expression on peripheral CD14+ monocytes was analyzed in HBV-ACLF patients. CD14+ monocytes-induced cytotoxicity and CD14+ monocytes-mediated T cell activation in response to CD100 stimulation was also assessed in direct and indirect contact coculture culture systems. HBV-ACLF patients had lower plasma sCD100 and higher mCD100 level on CD14+ monocytes compared with asymptomatic HBV carriers, chronic hepatitis B patients, and controls. CD14+ monocytes from HBV-ACLF patients induced limited target Huh7.5 cell death and secreted less interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and granzyme B in both direct and indirect contact coculture systems compared with controls. Recombinant sCD100 not only enhanced CD14+ monocytes-mediated Huh7.5 cell death and granzyme B secretion, but it also elevated CD14+ monocytes-induced IFN-γ/interleukin-17 production by CD4+ T cells as well as IFN-γ/TNF-α secretion by CD8+ T cells in HBV-ACLF patients. The current data indicated that severe inflammation induced sCD100/mCD100 imbalance to inactivate CD14+ monocytes response, which might be beneficial for the survival of HBV-ACLF patients.

Keywords: CD100; acute-on-chronic liver failure; hepatitis B virus; immune regulation; monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-On-Chronic Liver Failure* / metabolism
  • Acute-On-Chronic Liver Failure* / pathology
  • CD8-Positive T-Lymphocytes
  • Hepatitis B virus
  • Hepatitis B, Chronic*
  • Humans
  • Monocytes