These findings support the contribution of CYP2E1-mediated TCE metabolism in autoimmune response and an important role of Nrf2 pathway in TCE-mediated autoimmunity.
While activation of Nrf2 signaling is known to exert anti-inflammatory effects, Nrf2 function in inflammation-mediated autoimmune disorders, such as type 1 diabetes, is not well established.
Moreover, MLT inhibits NF-κB signaling pathway to reduce TNF-α and IL-1β expression, promotes Nrf2 gene and protein expression to reduce oxidative and inflammatory states and regulates Bax and Bcl-2 to reduce apoptosis; all of which alleviate the development of autoimmune diseases.
We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting.
Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis.
Activation of cytoprotective Nrf2/ARE-regulated genes can suppress inflammatory responses, whereas decreased expression of these genes results in autoimmune disease and enhanced inflammatory responses to oxidant insults.