Redox imbalance in T cell-mediated skin diseases

Abstract

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

Figure 1

Sources and responses to reactive oxygen and nitrogen species (ROS and RNS) in the skin. These highly reactive entities are generated as a result of normal intracellular metabolism in mitochondria and peroxisomes, and by a variety of cytosolic enzyme systems. The skin is peculiarly rich of enzymatic and nonenzymatic systems for the regulation of overall ROS and RNS levels and hence for the maintenance of physiological homeostasis, due to its direct contact with strong pro-oxidative physical and chemical insults from the environment. These include UV and ionizing radiations, and a variety of pollutants. During chronic inflammatory events, the persistent release of potent cytokines by infiltrating leukocytes contribute to perturb the redox balance, essentially through the upregulated expression of numerous enzymes involved in the regulation of this balance. Lower-than-normal levels of ROS and RNS leads to impaired cell proliferation and reduced host defence. Also an increase in their levels is detrimental for the skin, leading to damage to cell components and eventually acceleration of ageing and age-related diseases.