TIGIT negatively regulates inflammation by altering macrophage phenotype

(PVR), the receptor of TIGIT, was dramatically upregulated on the surface of mouse peritoneal macrophages when exposed to LPS. TIGIT-Fc fusion protein not only inhibited the macrophage activation, but also skewed M1/M2 balance toward an anti-inflammatory profile, especially enhanced the secretion of IL-10. The activation of TIGIT/PVR pathway in macrophages correlated with increased nuclear translocation of c-Maf, which promotes IL-10 transcription. Treatment with fibroblasts stably secreting TIGIT-Fc fusion protein significantly reversed the lethal and sublethal endotoxic shock, which facilitated peritoneal macrophages to switch towards anti-inflammatory M2 cytokine profiles. These findings highlight a novel role of the TIGIT/PVR pathway in macrophage M2 polarization and suggest that TIGIT may have the potential to optimize the treatment of macrophage-involved inflammatory diseases.