Nrf2 as regulator of innate immunity: A molecular Swiss army knife!

Organisms are constantly exposed to a broad range of pathological and stress-inducing agents, allergens and environmental chemicals that can induce infections, toxicity or other undesirable reactions. Our immune system has evolved over time in order to efficiently respond to these exogenous insults and maintain homeostasis. In particular, the innate immune system acts as primary barrier to prevent the entrance of invasive agents or allergens. This system is comprised of a diversity of cell types that are rapidly activated by recognition of common structures present in many potential pathogens known as pathogen-associated molecular patterns (PAMPs). The nuclear factor erythroid 2 related factor 2 (Nrf2) is a relevant basic leucine zipper (bZIP) transcription factor that is essential in the regulation of cell cycle homeostasis, cytoprotection, and innate immunity when cells are under stressful conditions. Although the role of Nrf2 in activating the expression of protective genes - such as antioxidant or anti-inflammatory - is known, its role in innate immunity and immune-related gene expression remains not yet clear. The present review summarizes current knowledge on Nrf2 signaling pathway structure and activity under both physiological state and upon oxidative stress. In addition, the relation between Nrf2 signaling pathway and the innate immune system is discussed, highlighting the potential therapeutic effects of diverse natural and synthetic compounds as Nrf2 regulators.