Regulation of oral immune tolerance by the microbiome in food allergy.
Regulation of oral immune tolerance by the microbiome in food allergy.
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DOI：
10.1016/j.coi.2019.06.001
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发表时间：
2019-10
影响因子：
7
通讯作者：
Emmanuel Stephen-Victor;T. Chatila
中科院分区：
文献类型：
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作者：
Emmanuel Stephen-Victor;T. Chatila
亮点食物过敏 (FA) 的特点是致病性菌群失调。FA 中的菌群失调通过损害 ROR-γt+ 诱导的调节性 T 细胞的生成，破坏对饮食抗原的口服耐受性。梭状芽胞杆菌和拟杆菌共生菌治疗可激活新生 iTreg 细胞中的 MyD88-ROR-γt 轴，以恢复 FA 的免疫耐受。食物过敏 (FA) 的发病率和患病率急剧上升过去几十年来，人们的注意力集中在促进疾病的环境机制上，其中最主要的是微生物组。最近的研究现已证实，FA 中存在致病性生态失调，这种失调可能是由各种环境损害引起的，其中包括抗生素的使用和给药方式，这些损害会破坏增强对饮食抗原耐受性的免疫调节反应。这种菌群失调的一个关键特征是梭状芽胞杆菌物种的丧失，这些细菌物种的作用是促进肠道中食物过敏原特异性新生调节性 T 细胞的形成。值得注意的是，不同的免疫保护性共生细菌，包括梭菌目和拟杆菌目成员，通过上游 MyD88 依赖性机制诱导新生 Treg 细胞中的转录因子 RORγt，以促进对饮食抗原的耐受性。该轴的激活因生态失调而受到破坏，可以通过治疗性微生物群的治疗来恢复。这些发现凸显了基于微生物群的新型方法预防和治疗 FA 流行的潜力。
HighlightsFood allergy (FA) is characterized by pathogenic dysbiosis.The dysbiosis in FA disrupts oral tolerance to dietary antigens by impairing the generation of ROR-γt+ induced regulatory T cells.Therapy with Clostridiales and Bacteroidales commensal bacteria activates a MyD88-ROR-γt axis in nascent iTreg cells to restore immune tolerance in FA.The steep rise in the incidence and prevalence of food allergy (FA) in the last few decades have focused attention of environmental mechanisms which act to promote disease, chief among which is the microbiome. Recent studies have now established the presence of pathogenic dysbiosis in FA that could be precipitated by a variety of environmental insults, including among others antibiotic usage and mode of delivery, that act to subvert the immune regulatory response that enforce tolerance to dietary antigens. A key attribute of this dysbiosis is the loss of Clostridial bacterial species that act to promote the formation of food allergen-specific nascent regulatory T cells in the gut. Significantly, different immunoprotective commensal bacteria, including members of the Clostridiales and Bacteroidales orders act to induce the transcription factor RORγt in nascent Treg cells via an upstream MyD88-dependent mechanism to promote tolerance to dietary antigens. Activation of this axis is disrupted by the dysbiosis, and can be restored by treatment with therapeutic microbiota. These findings highlight the potential for novel microbiota-based approaches to the prevention and treatment of the FA epidemic.