Allergen endotoxins induce T-cell-dependent and non-IgE-mediated nasal hypersensitivity in mice
Allergen endotoxins induce T-cell-dependent and non-IgE-mediated nasal hypersensitivity in mice
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DOI：
10.1016/j.jaci.2016.03.023
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发表时间：
2017-01-01
影响因子：
14.2
通讯作者：
Yoshimoto, Tomohiro
中科院分区：
文献类型：
--
作者：
Iwasaki, Naruhito;Matsushita, Kazufumi;Yoshimoto, Tomohiro
工作背景：过敏原介导的IgE在肥大细胞/嗜碱性粒细胞上的交联是1型过敏性疾病如过敏性鼻炎（AR）的公认触发因素。然而，过敏原可能不是AR的唯一触发因素，一些过敏样反应是由非IgE介导的机制诱导的。目的：我们试图描述一种新的非IgE介导的，内毒素引发的鼻1型过敏样反应在mice.Methods：为了研究是否内毒素影响打喷嚏responses，小鼠腹腔内免疫卵清蛋白（OVA），然后鼻腔内的挑战与内毒素或内毒素含有OVA。为了探讨T细胞的作用和内毒素诱导的反应的机制，小鼠过继转移与体外分化的卵清蛋白特异性T（H）2细胞，然后鼻腔攻击与内毒素的无或含有内毒素的卵清蛋白。结果：内毒素含有，但不是无内毒素，卵清蛋白引起的小鼠打喷嚏反应独立于IgE介导的信号。OVA特异性T（H）2细胞过继转移到小鼠中表明，抗原特异性T（H）2细胞的局部活化是应答所必需的。Toll样受体4-髓样分化因子88信号通路在含内毒素的OVA诱发的鼻炎中是不可或缺的。此外，LPS直接触发了OVA特异性T（H）2转移和鼻内毒素的OVA致敏小鼠的喷嚏反应。虽然抗组胺药抑制打喷嚏反应，但肥大细胞/嗜碱性粒细胞耗竭的小鼠对含内毒素的OVA有正常的打喷嚏反应。氯膦酸盐治疗废除内毒素含有OVA引起的鼻炎，这表明单核细胞/巨噬细胞在此responsibility.Conclusions的参与：抗原特异性鼻激活的CD 4 - 1 T细胞，然后由内毒素暴露诱导肥大细胞/嗜碱性粒细胞独立组胺释放的鼻子，elelevated打喷嚏反应。因此，环境或鼻腔驻留细菌可能会加剧AR症状。此外，这种新的现象可能解释目前未知的机制过敏（样）疾病。
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 T(H)2 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 T(H)2 cell adoptive transfer to mice demonstrated that local activation of antigen-specific T(H)2 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 T(H)2-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 1 T cells followed by endotoxin exposure induces mast cell/basophilindependent histamine release in the nose that elicits sneezing responses. Thus, environmental or nasal residential bacteria may exacerbate AR symptoms. In addition, this novel phenomenon might explain currently unknown mechanisms in allergic(-like) disorders.