Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Signaling in Oxidative Stress, Immunity, and Inflammatory Disorders

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a master transcriptional regulator that plays a central role in cellular defense mechanisms, particularly in combating oxidative stress. It exerts its effects by orchestrating the expression of a wide array of antioxidant, detoxifying, and cytoprotective genes, thereby maintaining redox homeostasis and protecting cells from oxidative damage. Beyond this classical role, growing evidence highlights the broader involvement of Nrf2 in regulating immune function and inflammatory responses. Through cross-talk with signaling pathways such as NF-κB and MAPKs, Nrf2 modulates the expression of cytokines, chemokines, and other inflammatory mediators, thereby influencing both innate and adaptive immunity. Dysregulation or impaired activation of Nrf2 has been implicated in the pathogenesis of several inflammatory and autoimmune disorders, including rheumatoid arthritis, multiple sclerosis, asthma, and chronic obstructive pulmonary disease. These findings underscore its relevance not only in oxidative stress responses but also in disease progression and immune regulation. Recent advances in pharmacology and nutraceutical research have identified small-molecule activators and natural compounds, such as polyphenols and isothiocyanates, that can enhance Nrf2 signaling. Harnessing these therapeutic strategies offers promising opportunities for controlling excessive inflammation and oxidative injury. Understanding the multifaceted roles of Nrf2 provides a foundation for novel interventions in chronic inflammatory diseases. Keywords: Nrf2, oxidative stress, inflammation, immunity, antioxidant response