IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling.
IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling.
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DOI：
10.1016/j.jaci.2010.11.009
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Oettgen HC
中科院分区：
文献类型：
--
作者：
Mathias CB;Hobson SA;Garcia-Lloret M;Lawson G;Poddighe D;Freyschmidt EJ;Xing W;Gurish MF;Chatila TA;Oettgen HC
在特应性个体中，食物摄入驱动IgE抗体的产生，其可引发超敏反应。IL-4通路在这种反应中起着关键作用，其组分中的遗传多态性与过敏有关。检测IL-4受体（IL-4 R）α链中的激活突变是否会增强对食物抗原的过敏反应。用卵清蛋白（OVA）灌胃F709小鼠，其中IL-4 R α免疫酪氨酸抑制基序（ITIM）失活。评估对OVA攻击的反应和免疫应答，包括抗体产生和Th 2应答。F709小鼠，而不是野生型（WT）对照，通过灌胃OVA和霍乱毒素（CT）或葡萄球菌肠毒素B（SE B）致敏，显示肥大细胞活化和全身过敏反应后，肠内挑战。甚至在仅用OVA肠内致敏的F709小鼠中也引起过敏反应。骨髓嵌合体实验证实，F709基因型所赋予的敏感性增加主要是由造血细胞介导的，但非造血细胞也有贡献。F709小鼠表现出对大分子的肠通透性增加。与WT小鼠相比，F709基因型赋予增加的OVA特异性IgE，但不赋予增加的IgG 1应答、局部和全身性Th 2应答和肠肥大细胞增生。在缺乏IgE或IgE高亲和力受体（FcεRI）的F709小鼠中，过敏反应被消除。增强的IL-4 R α信号传导可增加肠道通透性，并显著增强对食物过敏原的敏感性。与对注射抗原的过敏反应不同，在啮齿动物中，过敏反应可由IgE或IgG抗体介导，F709小鼠中的食物诱导反应仅为IgE依赖性。
In atopic individuals, food ingestion drives the production of IgE antibodies that can trigger hypersensitivity reactions. The IL-4 pathway plays critical roles in this response and genetic polymorphisms in its components have been linked to allergy. To test whether an activating mutation in the IL-4 receptor (IL-4R) α chain enhances allergic responses to a food antigen. F709 mice, in which the IL-4Rα immuno-tyrosine inhibitory motif (ITIM) motif is inactivated, were gavage fed with ovalbumin (OVA). Reactions to OVA challenge and immune responses including antibody production and Th2 responses were assessed. F709 mice, but not wild-type (WT) controls, sensitized by gavage with OVA and either cholera toxin (CT) or Staphylococcal enterotoxin B (SEB), displayed mast cell activation and systemic anaphylaxis upon enteral challenge. Anaphylaxis was elicited even in F709 mice enterally sensitized with OVA alone. Bone marrow chimera experiments established that the increased sensitivity conferred by the F709 genotype was mediated mostly by hematopoietic cells but that nonhematopoietic cells also contributed. F709 mice exhibited increased intestinal permeability to macromolecules. The F709 genotype conferred increased OVA-specific IgE but not IgG1 responses, local and systemic Th2 responses and intestinal mast cell hyperplasia as compared with WT mice. Anaphylaxis was abrogated in F709 mice lacking IgE or the high affinity receptor for IgE (FcεRI). Augmented IL-4Rα signaling confers increased intestinal permeability and dramatically enhanced sensitivity to food allergens. Unlike anaphylaxis to injected antigens, which in rodents can be mediated by either IgE or IgG antibodies, the food-induced response in F709 mice is solely IgE-dependent.
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影响因子：
5.4
作者：
Faulkner, H;Humphreys, N;Grencis, R
通讯作者：
Grencis, R
DOI：
10.4049/jimmunol.0901471
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jones TG;Hallgren J;Humbles A;Burwell T;Finkelman FD;Alcaide P;Austen KF;Gurish MF
通讯作者：
Gurish MF
影响因子：
14.2
作者：
Khodoun, Marat;Strait, Richard;Orekov, Tatyana;Hogan, Simon;Karasuyama, Hajime;Herbert, De'Broski R.;Koehl, Joerg;Finkelman, Fred D.
通讯作者：
Finkelman, Fred D.
影响因子：
14.2
作者：
Li, XM;Schofield, BH;Sampson, HA
通讯作者：
Sampson, HA
影响因子：
30.5
作者：
Dardalhon, Valerie;Awasthi, Amit;Kwon, Hyoung;Galileos, George;Gao, Wenda;Sobel, Raymond A.;Mitsdoerffer, Meike;Strom, Terry B.;Elyaman, Wassim;Ho, I-Cheng;Khoury, Samia;Oukka, Mohamed;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.