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.
【저자키워드】 Monocytes, immune regulation, Hepatitis B virus, Acute-on-chronic liver failure, CD100,