Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA; Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Department of Pharmacology and Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Redox Biol. 2024 Apr;70:103077. doi: 10.1016/j.redox.2024.103077. Epub 2024 Feb 10.
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.
炎症性疾病因其广泛的流行和对患者生活的严重影响而构成严重的健康挑战。为了减轻这些疾病的负担,核因子红细胞 2 相关因子 2(Nrf2)已成为一个关键的参与者。作为一种密切参与细胞对抗代谢和氧化应激的转录因子,Nrf2 调节免疫细胞炎症反应的作用引起了广泛关注。最近的发现表明,Nrf2 改变细胞氧化还原状态的能力是其对免疫反应的调节作用的基础。我们的综述深入探讨了临床前和临床证据,这些证据强调了 Nrf2 激活剂对免疫细胞表型的复杂影响,特别是在炎症环境中。通过对 Nrf2 在不同免疫细胞群中的作用进行详细分析,我们揭示了 Nrf2 激活剂在塑造免疫反应向更受调节状态的潜力,通过模拟免疫细胞的氧化还原状态来减轻炎症的不良影响。此外,我们还探讨了纳米封装技术的创新应用,该技术增强了 Nrf2 激活剂的递送和功效,可能为炎症性疾病的治疗策略带来新的突破。我们希望本综述将激发 Nrf2 靶向治疗的发展和扩展,这可能会显著改善广大炎症性疾病患者的治疗效果。