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However, their involvement in allergic rhinitis remains unclear. Thus, in this study, we aimed to clarify the role of ILC2s and acquired immune responses in the onset of allergic rhinitis induced via intranasal mucosal sensitization with antigens in mice. Naive mice were intranasally administered antigens in the short term (4 consecutive days) or long term (21 consecutive days). The number of sneezes, serum-specific immunoglobulin E (IgE) levels, and eosinophil infiltration in the nasal mucosa were subsequently assessed. Short-term intranasal antigen administration to naive mice induced eosinophilic inflammation of the nasal mucosa in an acquired immune-independent and protease- and ILC2-dependent manner. Antigen-independent sneezing was caused by a calcium influx response via transient receptor potential vanilloid channels. In contrast, long-term intranasal mucosal sensitization with antigens led to the onset of allergic rhinitis. Furthermore, increased serum-specific IgE levels and sneezing frequency, as well as significant eosinophilic infiltration, were observed in the nasal mucosa. ILC2s in the nasal mucosa did not proliferate upon short-term stimulation with antigens but proliferated upon long-term stimulation, facilitating acquired immunity and allergic rhinitis onset. Our findings demonstrated that allergic inflammation is induced by the protease\/IL-33\/ILC2\/IL-5 axis during the initiator phase. Acquired immunity induced by long-term sensitization and innate immunity facilitated by short-term sensitization together induce significant allergic inflammation and allergic rhinitis onset.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf060","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T12:02:24Z","timestamp":1759406544000},"page":"172-184","source":"Crossref","is-referenced-by-count":4,"title":["Role of Group 2 innate lymphoid cells in intranasal sensitization-induced allergic rhinitis in mice"],"prefix":"10.1093","volume":"38","author":[{"given":"Yukinori","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medical Science, University of Fukui , 23-3, Shimoaizuki, Matsuoka Eiheiji-cho, Yoshida-gun, Fukui 910-1193 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