Cutting Edge: Nqo1 Regulates Irritant Contact Hypersensitivity against Croton Oil through Maintenance of Dendritic Epidermal T Cells

Irritant contact dermatitis (ICD) is associated with local release of inflammatory mediators such as reactive oxygen species and regulated by various antioxidative enzymes and antioxidants. Although Nqo1 is involved in antioxidative reactions and detoxification, its role in ICD remains unknown. Nqo1-deficient mice exhibited augmented ear swelling accompanied by neutrophil infiltration in the croton oil-induced mouse ICD model. In the skin of Nqo1-deficient mice, V gamma 5Vd1 + dendritic epidermal T cells (DETCs), which are known to suppress ICD, were severely reduced. As the transfer of DETCs into Nqo1-deficient mice reversed an increased ICD response, loss of DETCs could account for the increased ICD. DETCs from Nqo1-deficient mice were sensitive to oxidative stress-induced cell death in vitro, and antioxidant NAC treatment in the ears of these mice rescued the number of DETCs and produced a normal ICD response. Taken together, the current results demonstrate that antioxidative enzyme Nqo1 regulates ICD through DETC maintenance.