Schematic representation of the postulated vanin-1 pathway in human blood cells in response to oxidative stress. This figure summarizes our hypothesis based on the work of Berruyer et al^8,24  and our findings. The steps with experimental data support are highlighted in the box. An inciting event (eg, infection) induces generation of free radical species, whereas ROS has a positive modulatory role in immune activation and eradication of viral infections, excessive ROS, or inadequate capability of antioxidant scavengers leads to an oxidative stress state. In the presence of oxidative stress, antioxidant response-like elements within the promoter region of VNN1 act as stress-regulated targets and enhance VNN1 expression. More cysteamine is produced from hydrolysis of pantetheine; cysteamine is then converted to cystamine, which is an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme of glutathione synthesis. Thus, the glutathione store as well as the GSH/GSSG ratio decrease, which subsequently intensifies the oxidative stress. On the other hand, the anti-inflammatory checkpoint PPARγ is also antagonized by cystamine; and as a result, more inflammatory cytokines and chemokines are produced.