Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation. Issue 5 (29th January 2020)

• Record Type: Journal Article
• Authors: Korotchenko, Evgeniia; Moya, Raquel; Scheiblhofer, Sandra; Joubert, Isabella A; Horejs‐Hoeck, Jutta; Hauser, Michael; Calzada, David; Iraola, Víctor; Carnés, Jerónimo; Weiss, Richard
• Is Part Of: Allergy. Volume 75:Issue 5(2020)
• Page Start: 1217
• Page End: 1228
• Publication Date: 2020-01-29
• Subjects: depigmented extract -- epicutaneous immunotherapy -- house dust mite -- laser -- skin immunization; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14164
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: Skin‐based immunotherapy of type 1 allergies has recently been re‐investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)‐induced lung inflammation to explore the potential of laser‐facilitated epicutaneous allergen‐specific treatment. Methods: Mice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented D pteronyssinus extract via laser‐generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole‐body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM‐specific IgG subclass antibodies were determined by ELISA. Serum as well as cell‐bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry. Results: Immunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred. Conclusion: Allergen‐specific immunotherapy with depigmented HDM extract via laser‐generated skin micropores offers a safe and effective treatment option for HDM‐induced allergy and lung inflammation. Abstract : Epicutaneous immunization via laser‐generated micropores is more potent than subcutaneous injection in induction of regulatory T cells and suppression of cytokines. EPIT induces higher levels of blocking IgG and less as well as shorter‐lived therapy‐associated IgE compared to SCIT with or without alum. EPIT suppresses airway hyperresponsiveness and lung inflammation in mice. Abbreatiations: EPIT, epicutaneous immunotherapy; SCIT, subcutaneous immunotherapy