Peanut-induced intestinal allergy is mediated through a mast cell-IgE-FcepsilonRI-IL-13 pathway.
Peanut-induced intestinal allergy is mediated through a mast cell-IgE-FcepsilonRI-IL-13 pathway.
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DOI：
10.1016/j.jaci.2010.05.017
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发表时间：
2010-08
影响因子：
14.2
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
--
作者：
Wang, Meiqin;Takeda, Katsuyuki;Shiraishi, Yoshiki;Okamoto, Masakazu;Dakhama, Azzeddine;Joetham, Anthony;Gelfand, Erwin W.
虽然与疾病有关，但FcεRI和IL-13对花生诱导的肠变态反应的发病机制的具体贡献尚未明确。确定FcεRI、IL-13和肥大细胞在花生诱导的肠过敏小鼠模型中肠粘膜反应发展中的作用。致敏野生型（WT）、Fcε RI缺陷型（FcεRI−/−）和肥大细胞缺陷型（KitW-sh/W-sh）小鼠每天口服花生，持续1周。将WT、FcεRI−/−、IL- 4−/−、IL-13−/−和IL- 4/IL-13−/−小鼠的骨髓源性肥大细胞（BMMC）分化并转移至WT、FcεRI−/−和KitW-sh/W-sh受体中。将来自WT和UBI-GFP/BL 6小鼠的BMMC分化并转移到WT和KitW-sh/W-sh小鼠中。使用IL-13 Ra 2-IgG融合蛋白实现了IL-13的阻断。FcεRI−/−小鼠显示肠道炎症（肥大细胞和嗜酸性粒细胞数量）和杯状细胞化生减少，空肠中IL-4、IL-6、IL-13和IL-17 A mRNA表达水平降低。与转移FcεRI−/−、IL-13−/−或IL-4/IL-13−/−BMMC相比，将WT BMMC转移给Fc εRI−/−受体恢复了其发生肠道过敏反应的能力。FcεRI−/−小鼠表现出较低的IL-13水平，用IL-13 R α2治疗WT小鼠可预防花生诱导的肠道过敏和炎症。这些数据表明，花生诱导的肠道过敏的发生是通过肥大细胞依赖性IgE-FcεRI-IL-13途径介导的。靶向IL-13可能是肠内IgE介导的花生过敏反应的潜在治疗方法。
Although implicated in the disease, the specific contributions of FcεRI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined. To determine the contributions of FcεRI, IL-13, and mast cells to the development of intestinal mucosal responses in a mouse model of peanut-induced intestinal allergy. Sensitized wild-type (WT), FcεRI-deficient (FcεRI−/−), and mast cell-deficient (KitW-sh/W-sh) mice received peanut orally every day for 1 week. Bone marrow-derived mast cells (BMMC) from WT, FcεRI−/−, IL- 4−/−, IL-13−/−, and IL- 4/IL-13−/− mice were differentiated and transferred into WT, FcεRI−/−, and KitW-sh/W-sh recipients. BMMC from WT and UBI-GFP/BL6 mice were differentiated and transferred into WT and KitW-sh/W-sh mice. Blockade of IL-13 was achieved using IL- 13Ra2-IgG fusion protein. FcεRI−/− mice showed decreased intestinal inflammation (mast cell and eosinophil numbers) and goblet cell metaplasia, and reduced levels of IL-4, IL-6, IL-13, and IL-17A mRNA expression in the jejunum. Transfer of WT BMMC to FcεRI−/− recipients restored their ability to develop intestinal allergic responses compared to transfer of FcεRI−/−, IL-13−/−, or IL-4/IL-13−/−BMMC. FcεRI−/− mice exhibited lower IL-13 levels and treatment of WT mice with IL-13Rα2 prevented peanut-induced intestinal allergy and inflammation. These data indicate that the development of peanut-induced intestinal allergy is mediated through a mast cell-dependent, IgE-FcεRI-IL-13 pathway. Targeting IL-13 may be a potential treatment for IgE-mediated peanut allergic responses in the intestine.
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影响因子：
14.2
作者：
Bock, SA;Muñoz-Furlong, A;Sampson, HA
通讯作者：
Sampson, HA
影响因子：
4.8
作者：
Hunt, James;Bracher, Marguerite G.;Beavil, Andrew J.
通讯作者：
Beavil, Andrew J.
影响因子：
64.8
作者：
Galli, Stephen J.;Tsai, Mindy;Piliponsky, Adrian M.
通讯作者：
Piliponsky, Adrian M.
DOI：
10.1084/jem.189.10.1565
发表时间：
1999-05-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McKenzie GJ;Fallon PG;Emson CL;Grencis RK;McKenzie AN
通讯作者：
McKenzie AN
影响因子：
15.9
作者：
Dombrowicz, D;Flamand, V;Kinet, JP
通讯作者：
Kinet, JP