Proteolytic activity accelerates the T_H17/T_H22 recall response to an epicutaneous protein allergen-induced T_H2...

Epicutaneous exposure to protein allergens, such as papain, house dust mite (HDM), and ovalbumin (OVA), represents an important mode of sensitization for skin diseases including protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. These diseases are inducible by re-exposure to an allergen at both original skin sensitization and distant skin sites. In this study, we examined the serum IgE/IgG₁ response, differentiation of T-helper (T_H) cells, and epicutaneous T_H recall response in mice pre-sensitized with protein allergens through the back skin and subsequently challenged on the ear skin. Repeated epicutaneous sensitization with allergenic proteins including papain, HDM, OVA, and protease inhibitor-treated papain, but not bovine serum albumin, induced serum allergen-specific antibody production, passive cutaneous anaphylaxis responses, and T_H2 differentiation in the skin draining lymph node (DLN) cells. Sensitization with papain or HDM, which have protease activity, resulted in the differentiation of T_H17 as well as T_H2. In papain- or HDM-sensitized mice, a subsequent single challenge on the ear skin induced the expression of T_H2 and T_H17/T_H22 cytokines. These results suggest that allergenic proteins induce the differentiation of T_H2 in skin DLN cells and an antibody response. These findings may be useful for identifying proteins of high and low allergenic potential. Moreover, allergenic proteins containing protease activity may also differentiate T_H17 and induce T_H2 and T_H17/T_H22 recall responses at epicutaneous challenge sites. This suggests that allergen protease activity accelerates the onset of skin diseases caused by protein allergens.