Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Inflammatory diseases present a serious health challenge due to their widespread prevalence and the severe impact on patients' lives. In the quest to alleviate the burden of these diseases, nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a pivotal player. As a transcription factor intimately involved in cellular defense against metabolic and oxidative stress, Nrf2's role in modulating the inflammatory responses of immune cells has garnered significant attention. Recent findings suggest that Nrf2's ability to alter the redox status of cells underlies its regulatory effects on immune responses. Our review delves into preclinical and clinical evidence that underscores the complex influence of Nrf2 activators on immune cell phenotypes, particularly in the inflammatory milieu. By offering a detailed analysis of Nrf2's role in different immune cell populations, we cast light on the potential of Nrf2 activators in shaping the immune response towards a more regulated state, mitigating the adverse effects of inflammation through modeling redox status of immune cells. Furthermore, we explore the innovative use of nanoencapsulation techniques that enhance the delivery and efficacy of Nrf2 activators, potentially advancing the treatment strategies for inflammatory ailments. We hope this review will stimulate the development and expansion of Nrf2-targeted treatments that could substantially improve outcomes for patients suffering from a broad range of inflammatory diseases.