Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation.
Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation.
复制标题
DOI：
10.1016/j.jaci.2018.02.003
复制
发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Cook-Mills JM
中科院分区：
文献类型：
--
作者：
Walker MT;Green JE;Ferrie RP;Queener AM;Kaplan MH;Cook-Mills JM
新生儿食物过敏发生的机制尚不清楚，但在患者群体中，显然与皮肤屏障缺陷的遗传易感性有关。皮肤屏障缺陷是否在功能上促进了食物过敏的发展尚不清楚。该研究的目的是确定患者群体中主要为杂合的皮肤屏障突变是否有助于食物过敏的发展。Flgft和Tmem79ma突变杂合的小鼠对环境过敏原和食物过敏原皮肤致敏。致敏后，小鼠口服食物过敏原，然后测量炎症、炎症介质和过敏反应。我们定义了在短暂的皮肤暴露于食物和环境过敏原后皮肤屏障突变的新生小鼠的炎症、炎症介质和食物过敏原诱导的过敏反应的发展。此外，过敏母亲的新生儿对食物过敏原的次优致敏反应升高。重要的是，这些新生小鼠对食物过敏原的反应依赖于皮肤屏障功能的遗传缺陷和暴露于环境过敏原。在皮肤致敏过程中阻断ST2可抑制过敏反应、抗原特异性IgE和炎症介质的发展。新生儿的过敏反应和抗原特异性IgE也被口服预先暴露于食物过敏原所抑制，但有趣的是，这被同时预先暴露于皮肤环境过敏原所钝化。这些研究揭示了新生小鼠食物过敏致敏和过敏反应的机制，这些机制与人类早期生活暴露和临床食物过敏遗传学的特征一致，并证明屏障功能的改变驱动了对食物过敏原的过敏反应的发展。
Mechanisms for the development of food allergy in neonates are unknown but are clearly linked in patient populations to a genetic predisposition towards skin barrier defects. Whether skin barrier defects functionally contribute to development of food allergy is unknown. The purpose of the study was to determine whether skin barrier mutations, that are primarily heterozygous in patient populations, contribute to the development of food allergy. Mice heterozygous for the Flgft and Tmem79ma mutations were skin sensitized with environmental allergens and food allergens. After sensitization, mice received oral challenge with food allergen and then inflammation, inflammatory mediators, and anaphylaxis were measured. We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations following brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have elevated responses to suboptimal sensitization with food allergens. Importantly, the responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. Blockade of ST2 during skin sensitization inhibited development of anaphylaxis, antigen-specific IgE and inflammatory mediators. The neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen but, interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early life exposures and genetics in clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen.
登录
查看更多内容
DOI：
10.1016/j.jaci.2011.01.031
发表时间：
2011-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brown SJ;Asai Y;Cordell HJ;Campbell LE;Zhao Y;Liao H;Northstone K;Henderson J;Alizadehfar R;Ben-Shoshan M;Morgan K;Roberts G;Masthoff LJ;Pasmans SG;van den Akker PC;Wijmenga C;Hourihane JO;Palmer CN;Lack G;Clarke A;Hull PR;Irvine AD;McLean WH
通讯作者：
McLean WH
影响因子：
12.4
作者：
Baek, J. O.;Roh, J. Y.;Jung, Y.
通讯作者：
Jung, Y.
影响因子：
5.9
作者：
Carlsten, Chris;Dimich-Ward, Helen;Chan-Yeung, Moira
通讯作者：
Chan-Yeung, Moira
DOI：
10.1165/rcmb.2009-0400oc
发表时间：
2011-03-01
影响因子：
6.4
作者：
Fedulov, Alexey V.;Kobzik, Lester
通讯作者：
Kobzik, Lester
DOI：
10.1152/ajplung.00301.2015
发表时间：
2016-04-15
影响因子：
4.9
作者：
Abdala-Valencia, Hiam;Soveg, Frank;Cook-Mills, Joan M.
通讯作者：
Cook-Mills, Joan M.