Establishment of IL-33 plus TSLP-induced human steroid-resistant asthma model using humanized mice and its potential application in preclinical research

Le résumé fourni par la source

Background: The mechanism of steroid-resistant asthma remains unclear because of the difficulty of directly analyzing the lungs of patients. We have already established a human asthma model using humanized human (h) IL-3/hGM-CSF/hIL-5 Transgenic NOG mice, which can differentiate into human immune cells after human stem cell transplantation. We also reported on the generation of a steroid-resistant asthma model using humanized mice at ATS 2019. Benralizumab, an anti-IL-5 receptor monoclonal antibody, has shown efficacy in the treatment of steroid-resistant asthma in real-world clinical practice. In this study, the efficacy of Benralizumab in suppressing human eosinophilic inflammation was verified in a steroid-resistant asthma model using humanized mice. Methods: A humanized mice model of steroid-resistant asthma was generated by administration of recombinant (r) human (h) IL-33, rhTSLP and dexamethasone (ATS, 2019). Then, we administered Benralizumab via the intraperitoneal route from day 0 to 3, to a humanized mice model of steroid-resistant asthma. On day 7, we collected the bronchoalveolar lavage fluids (BALFs) and lung tissue and measured airway eosinophilic inflammation and goblet cell hyperplasia. Results: Benralizumab suppressed rhIL-33+rhTSLP-induced human eosinophilic inflammation, hEDN production in the BALFs, airway inflammation in lung tissues but not goblet cell hyperplasia. Conclusions: Benralizumab suppressed steroid-resistance human eosinophilic inflammation. This model has potential for use as a preclinical model.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.