Irritant contact dermatitis is regulated by antioxidative enzyme NAD(P)H:quinone oxidoreductase (Nqo1).

Abstract

Abstract Irritant contact dermatitis (ICD) is the most common occupational skin inflammatory disorder caused by the exposure of chemical or physical irritants. Local release of inflammatory mediators such as cytokines, lipid mediators, and reactive oxygen species (ROS) are known to be important in the establishment of ICD. Antioxidative enzymes such as Nqo1 are known to be responsible for the degradation of ROS. Therefore, in the current study, we focused on the involvement of Nqo1 in ICD. In the mouse ICD model using croton oil, we found that Nqo1-deficient mice exhibited increased ear swelling and augmented expression of proinflammatory cytokines such as IL-6 and IL-17A in the skin. As we expected, it is indicated that Nqo1 has protective role against ICD. However, it is not applicable for general inflammatory responses, because the knockout mice showed unaltered response in the allergic contact dermatitis mouse model. Interestingly, we found that severe reduction of Vγ5Vδ1+ dendritic epidermal T cells (DETCs) in the skin of Nqo1 deficient mice, which are reported to inhibit ICD. Transfer of DETCs into RAG−/− mice revealed impaired survival of Nqo1-deficient DETCs. In addition, Nqo1-deficient DETCs were sensitive to oxidative stress-induced cell death, and anti-oxidant NAC treatment rescued decreased DETCs in Nqo1-deficient mice. These results suggest that Nqo1 regulates ICD through DETC development and/or homeostasis, possibly by antioxidative function.