The Potential of Nrf2 Activation as a Therapeutic Target in Systemic Lupus Erythematosus

Inflammation and oxidative stress are well established in systemic lupus erythematosus (SLE) and are critical to the pathogenesis of autoimmune diseases. The transcription factor NF-E2 related factor 2 (Nrf2) is a central regulator of cellular anti-oxidative responses, inflammation, and restoration of redox balance. Accumulating reports support an emerging role for the regulation of Nrf2 in SLE. These include findings on the development of lupus-like autoimmune nephritis and altered immune cell populations in mice lacking Nrf2, as well as decreased Nrf2 abundance in the dendritic cells of patients with SLE. Nrf2-inducing agents have been shown to alleviate oxidative and inflammatory stress and reduce tissue injury in SLE mouse models. Since Nrf2 expression can be increased in activated T cells, the precise role of Nrf2 activation in different immune cell types and their function remains to be defined. However, targeting Nrf2 for the treatment of diseases associated with oxidative stress and inflammation, such as SLE, is promising. As investigation of Nrf2-inducing agents in clinical trials grows, defining the signaling and molecular mechanisms of action and downstream effects in response to different Nrf2-inducing agents in specific cells, tissues, and diseases, will be critical for effective clinical use.

Automated summary

Inflammation and oxidative stress play crucial roles in SLE, and Nrf2 is a central regulator of cellular anti-oxidative responses, inflammation, and redox homeostasis. Regulation of Nrf2 has been shown to have important implications in SLE, and Nrf2-inducing agents have demonstrated the potential to alleviate oxidative and inflammatory stress and reduce tissue injury. However, further research is needed to elucidate the specific role of Nrf2 activation in different immune cell types and its mechanisms of action.