Investigating the role of nuclear factor erythroid 2-related factor 2 pathway on T cell & endothelial cell-based in...

Autoimmune disease is a complex condition where the immune system mistakenly attacks healthy tissues and affects millions around the world. Although there is no definitive cure or effective treatment, targeting the interaction between leukocytes and vascular endothelium presents a promising strategy for reducing excessive immune infiltration. Among strategies, combating oxidative stress and inflammation by activating antioxidant and anti-inflammatory genes is the best solution to decrease immune filtration. Nuclear-factor-erythroid 2-related factor-2 (NRF2) is a key player regulating oxidative stress and inflammation. This study investigates the anti-inflammatory impacts of the NRF2 pathway on the activated T cells that nonspecifically induce endothelial inflammation. To explore this, the NRF2 pathway in Human Umbilical Vein Endothelial Cells (HUVEC) was induced by using two approaches: NRF2 gene overexpression through the lentiviral systems (NRF2OE) and synthetic inducer, tert-butyl hydroquinone (TBHQ). These types of conditioned cells were co-cultured with activated Jurkat T cells to evaluate any regulatory effects of the NRF2 protein. Here, we observed that NRF2OE HUVEC cells induced a possible phenotypic shift from pro-inflammatory Th1 cells to anti-inflammatory Treg cells through upregulation of IL10 expression and downregulation of IL2 and IL2RA. This shift may demonstrate that NRF2 and its downstream pathway may help regulate immune responses by enhancing immune tolerance and reducing inflammation. Overall, these findings highlight the NRF2 pathway as a powerful modulator of endothelial inflammation and indicate its potential as a valuable therapeutic target for treating autoimmune diseases.