{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:32:19Z","timestamp":1790015539425,"version":"4.0.1"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"21","funder":[{"name":"Grants-in-Aid for Scientific Research (S) from the Japan Society for the Promotion of Science","award":["2222007"],"award-info":[{"award-number":["2222007"]}]},{"name":"Grants-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science","award":["25430099"],"award-info":[{"award-number":["25430099"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,2]]},"abstract":"<jats:p>\n                    Asthma is one of the most common immunological diseases and is characterized by airway hyperresponsiveness (AHR), mucus overproduction, and airway eosinophilia. Although mouse models have provided insight into the mechanisms by which type-2 cytokines induce asthmatic airway inflammation, differences between the rodent and human immune systems hamper efforts to improve understanding of human allergic diseases. In this study, we aim to establish a preclinical animal model of asthmatic airway inflammation using humanized IL-3\/GM-CSF or IL-3\/GM-CSF\/IL-5 Tg NOD\/Shi-\n                    <jats:italic>scid<\/jats:italic>\n                    -IL2r\u03b3\n                    <jats:sup>null<\/jats:sup>\n                    (NOG) mice and investigate the roles of human type-2 immune responses in the asthmatic mice. Several important characteristics of asthma \u2014 such as AHR, goblet cell hyperplasia, T cell infiltration, IL-13 production, and periostin secretion \u2014 were induced in IL-3\/GM-CSF Tg mice by intratracheally administered human IL-33. In addition to these characteristics, human eosinophilic inflammation was observed in IL-3\/GM-CSF\/IL-5 Tg mice. The asthmatic mechanisms of the humanized mice were driven by activation of human Th2 and mast cells by IL-33 stimulation. Furthermore, treatment of the humanized mice with an anti\u2013human IL-13 antibody significantly suppressed these characteristics. Therefore, the humanized mice may enhance our understanding of the pathophysiology of allergic disorders and facilitate the preclinical development of new therapeutics for IL-33\u2013mediated type-2 inflammation in asthma.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.121580","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T17:12:57Z","timestamp":1540314777000},"source":"Crossref","is-referenced-by-count":41,"title":["A humanized mouse model to study asthmatic airway inflammation via the human IL-33\/IL-13 axis"],"prefix":"10.1172","volume":"3","author":[{"given":"Ryoji","family":"Ito","sequence":"first","affiliation":[{"name":"Central Institute for Experimental Animals (CIEA), Kanagawa, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Maruoka","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Nihon University School of Medicine, Tokyo, 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