Related Experiment Video
Updated: Jul 20, 2025
11:36
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
3.0K
DNAM-1 Immunoreceptor Protects Mice from Concanavalin A-Induced Acute Liver Injury by Reducing Neutrophil
Soichi Matsuo1,2, Tsukasa Nabekura3,4, Kenshiro Matsuda3,4
1Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Journal of Immunology (Baltimore, Md. : 1950)
|July 31, 2023
Summary
The DNAX accessory molecule-1 (DNAM-1) and CD155 interaction normally protects against acute liver injury. Loss of this pathway unexpectedly worsens liver damage by increasing neutrophil infiltration and inflammatory cytokines.
Area of Science:
- Immunology
- Hepatology
- Cellular Biology
Background:
- DNAX accessory molecule-1 (DNAM-1; CD226) is an activating immunoreceptor found on T cells and NK cells.
- The interaction between DNAM-1 and its ligand CD155 is crucial for innate and adaptive immune responses.
Purpose of the Study:
- To investigate the role of the DNAM-1-CD155 axis in Concanavalin A (Con A)-induced acute liver injury.
- To understand the mechanisms underlying T cell-mediated liver damage in the absence of DNAM-1.
Main Methods:
- Utilized DNAM-1-deficient (Cd226-/-) and wild-type (WT) mice models.
- Administered Con A to induce acute liver injury.
- Assessed liver injury severity, inflammatory cytokine levels (IL-6, TNF-α), neutrophil infiltration, and CXCL1 production.
- Performed co-culture experiments with hepatocytes and liver lymphocytes.
Main Results:
- DNAM-1-deficient mice showed exacerbated acute liver injury with higher IL-6 and TNF-α levels post-Con A injection compared to WT mice.
- Increased neutrophil infiltration was observed in the livers of Cd226-/- mice.
- Neutrophil depletion significantly ameliorated liver injury and reduced cytokine levels in Cd226-/- mice.
- Hepatocytes produced higher levels of CXCL1 in Cd226-/- mice, which was reduced by DNAM-1/CD155 interaction.
Conclusions:
- The DNAM-1-CD155 axis plays a protective role in Con A-induced acute liver injury.
- Loss of DNAM-1 signaling promotes neutrophil-mediated liver damage through increased CXCL1 production by hepatocytes.
- Targeting the DNAM-1-CD155 pathway may offer therapeutic potential for acute liver injury.
