Antigen protease activity on intact or tape-stripped skin induces acute itch and Th sensitization leading to airway eosinophilia in mice

Autor: Kimitsu, Toru, Kamijo, Seiji, Yoshimura, Tomoko, Masutani, Yurie, Shimizu, Saya, Takada, Keiko, Suchiva, Punyada, Ogawa, Hideoki, Okumura, Ko, Ikeda, Shigaku, Takai, Toshiro
Zdroj: JID Innovations; 20230101, Issue: Preprints
Abstrakt: Respiratory allergen sources such as house dust mites frequently contain proteases. We herein demonstrated that the epicutaneous application of a model protease antigen, papain, onto intact or tape-stripped ear skin of mice induced acute scratching behaviors and Th2, Th9, Th17/Th22 and/or Th1 sensitization in a protease activity-dependent manner. The protease activity of papain applied onto skin was also essential for subsequent airway eosinophilia induced by an intranasal challenge with low-dose papain. With tape stripping, papain-treated mice showed barrier dysfunction, the accelerated onset of acute scratching behaviors, and attenuated Th17/Th22 sensitization. In contrast, the protease activity of inhaled papain partially or critically contributed to airway atopic march responses in mice sensitized via intact or tape-stripped skin, respectively. These results indicated that papain protease activity on epicutaneous application via intact skin or skin with mechanical barrier damage is critical to the sensitization phase responses including acute itch and Th sensitization and progression to the airway atopic march, while dependency on the protease activity of inhaled papain in the atopic march differs by the condition of the sensitized skin area. The present study suggests that exogenous protease-dependent epicutaneous mechanisms are a target for controlling allergic sensitization and progression to the atopic march.
Databáze: Supplemental Index