A positive feedback loop reinforces the allergic immune response in human peanut allergy.
A positive feedback loop reinforces the allergic immune response in human peanut allergy.
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DOI：
10.1084/jem.20201793
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发表时间：
2021-07-05
期刊：
影响因子：
--
通讯作者：
Nadeau KC
中科院分区：
文献类型：
--
作者：
Zhou X;Yu W;Lyu SC;Macaubas C;Bunning B;He Z;Mellins ED;Nadeau KC
花生特异的CD4+T细胞驱动CD209+DC的分化，然后CD209+DC相互作用于相同的CD4+T细胞群，在正反馈循环中增加Th2细胞因子的表达。食物过敏是过敏反应的主要原因，涉及抗原递呈的细胞机制可能在其发病机制中发挥关键作用。然而，在食物过敏的背景下，特异性抗原提呈细胞(APC)亚群对食物过敏原的反应知之甚少。在这里，我们展示了花生过敏原通过过敏原特异性є+T细胞的作用来驱动CD209+单核细胞来源的树突状细胞(DC)和CD23+(Fc CD4RII)髓系树突状细胞的分化。CD209+DC在同一花生特异性的CD4+T细胞群上相互作用，在正反馈环路中增强Th2细胞因子的表达，这可能解释了已建立的食物过敏的持久性。为了支持这一新模型，我们在临床上证明，花生过敏患者口服免疫疗法(OIT)的开始与CD209+DC的减少有关，这表明打破正反馈的循环与治疗效果有关。
Peanut-specific CD4+ T cells drive the differentiation of CD209+ DCs, which then act reciprocally on the same CD4+ T cell population to increase Th2 cytokine expression in a positive feedback loop. Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells. CD209+ DCs act reciprocally on the same peanut-specific CD4+ T cell population to reinforce Th2 cytokine expression in a positive feedback loop, which may explain the persistence of established food allergy. In support of this novel model, we show clinically that the initiation of oral immunotherapy (OIT) in peanut-allergic patients is associated with a decrease in CD209+ DCs, suggesting that breaking the cycle of positive feedback is associated with therapeutic effect.
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