Investigating the role of NRF2 pathway on T cell & Endothelial cell based in vitro autoimmune disease model

Autoimmune diseases occur when the immune system attacks the body's own tissues mistakenly, resulting in tissue damage and chronic inflammation. These conditions are prevalent worldwide and can lead to a range of complications. A crucial factor in progression of autoimmune diseases is the interaction between leukocytes and endothelial cells. This interaction is fundamental to the inflammatory process. This study investigates antiinflammatory impacts of NRF2 pathway on the activated T cells that nonspecifically induce endothelial inflammation. It also aims to elucidate the role of oxidative stress and NRF2- mediated responses in modulating T cell interactions with endothelial cells, as well as to provide insights into the potential mechanisms underlying autoimmune diseases characterized by aberrant T cell binding and endothelial damage. In the current study, the NRF2 pathway was induced in Human Umbilical Vein Endothelial cells (HUVEC) utilizing NRF2 gene overexpression via lentiviral systems and the synthetic NRF2 inducer, tert-butyl hydroquinone (TBHQ). The effect of the NRF2 pathway on activated Jurkat cells were examined by direct co-culture with HUVEC in vitro. Underlying mechanisms were demonstrated with qPCR, human inflammatory cytokine cytometric bead array (CBA) and Immunocytochemistry (ICC). The NRF2-Overexpressed (NRF2OE) cell line demonstrated a 3-fold change of NRF2 gene compared to TBHQ group. In the NRF2OE HUVEC cells, only the SOD2 gene exhibited a significant fold change. Co-culture of NRF2OE HUVEC cells with activated Jurkat cells induced a phenotype shift from Th1 to Treg in Jurkat cells. Overall, these findings suggest that NRF2 pathway influences the interaction between endothelial cells and activated T cells, potentially altering T cell phenotypes and preventing firm adhesion of T cells. Further exploration could significantly advance the development of novel therapeutic strategies for autoimmune diseases and inflammatory conditions. By promoting the generation of Treg cells, NRF2 pathway has the potential to enhance immune tolerance, reduce autoimmune tissue damage, and improve outcomes in various inflammatory disorders.