教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Allergen endotoxins induce T-cell-dependent and non-IgE-mediated nasal hypersensitivity in mice. |
掲載誌名 | 正式名:The Journal of allergy and clinical immunology 略 称:J Allergy Clin Immunol ISSNコード:1097-6825(Electronic)0091-6749(Linking) |
掲載区分 | 国外 |
巻・号・頁 | 6749(16),pp.30146-4 |
著者・共著者 | Iwasaki Naruhito, Matsushita Kazufumi, Fukuoka Ayumi, Nakahira Masakiyo, Matsumoto oto, Akasaki Shoko, Yasuda Koubun, Shimizu Takeshi, Yoshimoto Tomohiro |
発行年月 | 2017/01 |
概要 | BACKGROUND:Allergen-mediated cross-linking of IgE on mast cells/basophils is a well-recognized trigger for type 1 allergic diseases such as allergic rhinitis (AR). However, allergens may not be the sole trigger for AR, and several allergic-like reactions are induced by non-IgE-mediated mechanisms.OBJECTIVE:We sought to describe a novel non-IgE-mediated, endotoxin-triggered nasal type-1-hypersensitivity-like reaction in mice.METHODS:To investigate whether endotoxin affects sneezing responses, mice were intraperitoneally immunized with ovalbumin (OVA), then nasally challenged with endotoxin-free or endotoxin-containing OVA. To investigate the role of T cells and mechanisms of the endotoxin-induced response, mice were adoptively transferred with in vitro-differentiated OVA-specific TH2 cells, then nasally challenged with endotoxin-free or endotoxin-containing OVA.RESULTS:Endotoxin-containing, but not endotoxin-free, OVA elicited sneezing responses in mice independent from IgE-mediated signaling. OVA-specific TH2 cell adoptive transfer to mice demonstrated that local activation of antigen-specific TH2 cells was required for the response. The Toll-like receptor 4-myeloid differentiation factor 88 signaling pathway was indispensable for endotoxin-containing OVA-elicited rhinitis. In addition, LPS directly triggered sneezing responses in OVA-specific TH2-transferred and nasally endotoxin-free OVA-primed mice. Although antihistamines suppressed sneezing responses, mast-cell/basophil-depleted mice had normal sneezing responses to endotoxin-containing OVA. Clodronate treatment abrogated endotoxin-containing OVA-elicited rhinitis, suggesting the involvement of monocytes/macrophages in this response.CONCLUSIONS:Antigen-specific nasal activation of CD4(+) T cells followed by endotoxin exposure induces mast cell/basophil-independent histamine release in the nose that elicits sneezing responses. Thus, environmental or nasal residential bacteria may exacerbate AR symptoms. In addit |
DOI | 10.1016/j.jaci.2016.03.023 |
PMID | 27287257 |