TIGIT negatively regulates inflammation by altering macrophage phenotype

Area of Science:

• Immunology
• Cell Biology

Background:

• Macrophages are key immune cells involved in inflammation.
• Lipopolysaccharide (LPS) exposure can lead to harmful inflammation via M1 macrophage polarization.
• Restoring macrophage polarization balance is crucial for treating inflammatory conditions.

Purpose of the Study:

• To investigate the role of the poliovirus receptor (PVR)/TIGIT pathway in macrophage polarization.
• To explore TIGIT as a therapeutic target for inflammatory diseases.

Main Methods:

• Assessed PVR upregulation on macrophages exposed to LPS.
• Utilized TIGIT-Fc fusion protein to modulate macrophage activation and polarization.
• Examined the effect of TIGIT/PVR pathway activation on c-Maf nuclear translocation.
• Evaluated the therapeutic efficacy of TIGIT-Fc secreting fibroblasts in an endotoxic shock model.

Main Results:

• Poliovirus receptor (PVR) was significantly upregulated on LPS-stimulated macrophages.
• TIGIT-Fc treatment inhibited macrophage activation and promoted an anti-inflammatory M2 profile, increasing IL-10 secretion.
• TIGIT/PVR pathway activation led to increased c-Maf nuclear translocation, enhancing IL-10 transcription.
• Fibroblast-delivered TIGIT-Fc reversed endotoxic shock by promoting M2 polarization.

Conclusions:

• The TIGIT/PVR pathway plays a novel role in promoting M2 macrophage polarization.
• Targeting the TIGIT/PVR pathway offers a potential strategy for treating inflammatory diseases involving macrophages.