Tolerogenic antigen-presenting cells successfully inhibit atopic dermatitis-like skin lesion induced by repeated epicutaneous exposure to ovalbumin.

Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that frequently begins at infancy and the majority of them develop asthma and/or allergic rhinitis later, in which food and inhaled allergens play an important role. There is a murine model for AD that is induced by repeated epicutaneous (e.c.) exposure with ovalbumin (OVA). This model shares many characteristic features with AD, including development of asthma as well as dermatitis. Recently, it is reported that ocular tolerance or tolerance induced by intravenous administration of in vitro generated tolerogenic antigen-presenting cells (tol-APC), which can bypasses ocular tolerance, inhibits the immune response in a murine asthma model. The present study was designed to investigate whether tolerance induced by tol-APC and ocular tolerance inhibits AD-like dermatitis induced by repeated e.c. sensitization with OVA. BALB/c mice were given a total of three 1 week e.c. exposures to OVA with 2-week intervals between exposures. After second exposure to OVA, mice received the tol-APC or received OVA in the anterior chamber (AC) of the eye (ocular tolerance). Both groups of mice received the tol-APC and mice that received OVA in the AC of the eye showed weakened cellular infiltration in the skin including eosinophils and mast cells, lower levels of antigen-specific IgE, lower levels of transcripts of IL-4, IL-5, IL-13 in the skin and less production of Th1 and Th2 cytokine by regional lymph node cells, compared with those of mice that received sham treatment and mice that received the tol-APC treated with unrelated antigen after second e.c. exposure to OVA. These results indicate that antigen-specific tolerance induced by the tol-APC and ocular tolerance can inhibit the dermatitis and its related systemic immune response in the murine AD model. These types of tolerance might lead to a new therapeutic approach to allergic skin disease.