Noti Mario, Kim Brian S, Siracusa Mark C, Rak Gregory D, Kubo Masato, Moghaddam Amin E, Sattentau Quentin A, Comeau Michael R, Spergel Jonathan M, Artis David
Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa.
J Allergy Clin Immunol. 2014 May;133(5):1390-9, 1399.e1-6. doi: 10.1016/j.jaci.2014.01.021. Epub 2014 Feb 20.
Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy.
We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy.
Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid.
Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease.
Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy.
通过受损的皮肤屏障接触食物过敏原已被认为是食物过敏患病率上升的一个潜在因素。
我们试图测试经皮致敏食物过敏原易引发肠道食物过敏的免疫机制。
在类似特应性皮炎的皮肤损伤处用卵清蛋白或花生对小鼠进行经皮致敏，随后进行胃内抗原激发。通过酶联免疫吸附测定法测量抗原特异性血清IgE水平和T(H)2细胞因子反应。使用实时聚合酶链反应测量肠道中2型细胞因子和肥大细胞蛋白酶的表达。通过流式细胞术检测皮肤中嗜碱性粒细胞和肠道中肥大细胞的聚集情况。通过对白喉毒素受体转基因（Baso-DTR）小鼠进行白喉毒素处理实现体内嗜碱性粒细胞耗竭。对于细胞转移研究，通过水动力尾静脉注射胸腺基质淋巴细胞生成素（TSLP）cDNA质粒在体内扩增嗜碱性粒细胞群体。
通过类似特应性皮炎的皮肤损伤对食物过敏原致敏与皮肤中TSLP诱导的嗜碱性粒细胞扩增有关，这些嗜碱性粒细胞促进抗原特异性T(H)2细胞因子反应、增加抗原特异性血清IgE水平以及肠道中肥大细胞的聚集，从而促进肠道食物过敏的发展。至关重要的是，TSLP反应的破坏或嗜碱性粒细胞的耗竭降低了对肠道食物过敏的易感性，而将TSLP诱导的嗜碱性粒细胞转移到完整皮肤中则促进了疾病的发生。
在受损皮肤屏障上的经皮致敏与TSLP诱导的嗜碱性粒细胞聚集有关，这些嗜碱性粒细胞对于促进抗原诱导的肠道食物过敏是必要且充分的。
