1. Introduction
Thioredoxin (Trx) is a ubiquitously expressed protein with a low molecular weight of 12 kDa; it composes the Trx system with NADPH and Trx reductase (TrxR).1 Trx has thiol-disulphide reductase activity that is affected by a highly conserved active site (-Cys32-Gly-Pro-Cys35-).2The reduced form of Trx transfers reducing equivalents to disulphides within the target molecules and catalyses their reduction. In this process, TrxR uses NADPH to reduce the active site disulphide to a dithiol in the Trx substrates3 (Figure 1a). Overall, the Trx system plays a critical role in regulating cellular redox balance through the reversible thiol-disulphide exchange reaction.
Trx1 is a major Trx isoform located in the cytoplasm that also translocates to the nucleus; it can directly scavenge reactive oxygen species (ROS) and thereby protects against oxidative stress.4In addition, Trx1 is involved in various redox-dependent cellular processes such as gene expression, signal transduction, cell growth and apoptosis, and it interacts with various target molecules.5 Under stress conditions, Trx1 is released into the extracellular space where it exerts a cytoprotective effect and has cytokine-like activities.6
Allergic diseases comprise a group of immune-mediated disorders that are mainly characterised by a Th2 immune response phenotype. In asthmatic patients in the attack stage, plasma Trx1 levels were found to be significantly higher than that those in the remission stage, and the level of Trx1 was substantially increased as the severity of the asthma attack increased.7 This suggests that Trx1 could be a useful clinical parameter with which to predict the progression of asthma.
The protective effects of Trx1 have been determined in relation to the pathogenesis of many human disorders including metabolic syndrome, and neurodegenerative, cardiovascular and inflammatory diseases.8-11 In this review, we focus on the findings of recent research into the underlying intercellular and intracellular mechanisms by which Trx1 regulates immune cells in response to allergic inflammatory diseases, such as allergic asthma, food and drug allergies, contact dermatitis and allergic rhinitis, as well as potential Trx-based therapeutic strategies for treatment of allergic diseases.